Esophageal Adenocarcinoma

MONDO:0005028 Pathograph 9 carcinoma of esophagus adenocarcinoma

Esophageal adenocarcinoma (EAC) is a gland-forming malignancy of the esophagus that usually arises in the distal esophagus from Barrett metaplastic mucosa after chronic gastroesophageal reflux. It is characterized by late clinical presentation, frequent TP53 alteration, chromosomal instability, and recurrent copy-number changes that can create targetable oncogenic subsets such as ERBB2-amplified disease.

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0
Mappings
0
Definitions
0
Inheritance
8
Pathophysiology
0
Histopathology
6
Phenotypes
9
Pathograph
4
Genes
4
Treatments
1
Subtypes
2
Differentials
2
Datasets
2
Trials
0
Models
12
References
1
Deep Research
🏷

Classifications

Harrison's Chapter
cancer solid tumor
ICD-O Morphology
Adenocarcinoma
◆

Subtypes

1
HER2-amplified esophageal adenocarcinoma
Molecular subset with ERBB2 amplification and HER2 overexpression that can be biomarker-selected for HER2-directed therapy.
Show evidence (1 reference)
PMID:21267790 SUPPORT Human Clinical
"True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression."
This directly supports a clinically relevant ERBB2-amplified molecular subset in esophageal adenocarcinoma.
⚙

Pathophysiology

8
GERD-Driven Esophageal Injury and Inflammation
Chronic gastroesophageal reflux exposes the esophageal mucosa to refluxate, producing mucosal inflammation and injury that sets the stage for Barrett metaplasia and later adenocarcinoma.
epithelial cell of esophagus link
esophagus link
Downstream
Barrett Esophagus Precursor State Persistent reflux injury promotes Barrett metaplasia.
Show evidence (2 references)
PMID:32119349 SUPPORT Human Clinical
"Gastroesophageal reflux disease (GERD) is a condition in which retrograde flow of stomach contents into the esophagus or beyond into other regions, eg, oral cavity, larynx, or the lungs, occurs, primarily resulting in inflammation of the esophageal mucosa."
This supports reflux-driven mucosal injury and inflammation as the initiating upstream process.
PMID:34503107 SUPPORT Human Clinical
"Barrett's esophagus (BE), a metaplastic response of the esophagus to gastro-esophageal reflux disease, is the main risk factor for the development of EAC. Almost all EACs are derived from BE."
This links chronic reflux to the metaplastic Barrett field that precedes EAC.
Barrett Esophagus Precursor State
Barrett esophagus is the principal precursor lesion for esophageal adenocarcinoma and provides the metaplastic epithelial field from which most EAC develops.
epithelial cell of esophagus link
esophagus link
Downstream
TP53 Somatic Mutation Barrett progression acquires tumor suppressor loss and increasingly unstable genomes.
Show evidence (2 references)
PMID:40874980 SUPPORT Human Clinical
"Barrett esophagus (BE) is the only known histological precursor to esophageal adenocarcinoma (EAC)."
This directly identifies Barrett esophagus as the precursor lesion to EAC.
PMID:34503107 SUPPORT Human Clinical
"Barrett's esophagus (BE), a metaplastic response of the esophagus to gastro-esophageal reflux disease, is the main risk factor for the development of EAC. Almost all EACs are derived from BE."
This links chronic reflux-driven Barrett metaplasia to the origin of most EACs.
TP53 Somatic Mutation
TP53 is the dominant recurrent tumor suppressor alteration in EAC and is commonly acquired during progression from Barrett dysplasia toward carcinoma.
epithelial cell of esophagus link
esophagus link
Downstream
Chromosomal Instability TP53 loss permits propagation of cell division errors as heritable chromosomal instability.
Show evidence (1 reference)
PMID:34503107 SUPPORT Human Clinical
"The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes."
This establishes TP53 mutation as the dominant recurrent genomic lesion in EAC.
Chromosomal Instability
Following TP53 loss, Barrett progression acquires multigenerational chromosomal instability with whole-genome duplication and complex copy-number rearrangements.
epithelial cell of esophagus link
DNA damage response link ⚠ ABNORMAL
esophagus link
Downstream
Copy-Number Driven Oncogenic Signaling Ongoing chromosomal instability generates amplifications and deletions that reinforce tumor growth signaling.
Show evidence (1 reference)
PMID:37794034 SUPPORT Human Clinical
"We identify distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss."
This supports ongoing chromosomal instability as a downstream consequence of p53 loss in Barrett progression and early EAC.
Copy-Number Driven Oncogenic Signaling
EAC carries a heavy burden of genomic rearrangements with amplifications and deletions, producing subsets with ERBB2 and other growth-pathway alterations that feed MAPK and PI3K-AKT signaling and tumor proliferation.
MAPK cascade link ↑ INCREASED phosphatidylinositol 3-kinase signaling link ↑ INCREASED cell population proliferation link ↑ INCREASED
esophagus link
Downstream
Chromosomal Instability-Linked Innate Immune and Myeloid Signaling Ongoing copy-number instability drives cGAS-linked inflammatory chemokine programs.
Show evidence (2 references)
PMID:34503107 SUPPORT Human Clinical
"EAC is characterized by a high burden of point mutations and genomic rearrangements, resulting in amplifications and deletions of genomic regions."
This supports copy-number-driven oncogenic signaling as a core feature of EAC genomes.
PMID:21267790 SUPPORT Human Clinical
"True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression."
This demonstrates a clinically relevant ERBB2-amplified subset within esophageal adenocarcinoma.
Chromosomal Instability-Linked Innate Immune and Myeloid Signaling
In chromosomally unstable EAC, innate immune sensing and chemokine signaling can recruit myeloid suppressor populations and create an immunosuppressive microenvironment.
myeloid cell link
innate immune response link ↑ INCREASED chemokine production link ↑ INCREASED
Downstream
Adaptive Immune Resistance Myeloid-dominated inflammatory signaling reinforces checkpoint-mediated immune escape.
Show evidence (2 references)
GEO:GSE316127 SUPPORT In Vitro
"Chromosomal instability (CIN), a pervasive feature of esophageal adenocarcinoma (EAC), drives tumor aggressiveness and metastasis."
This GEO-linked study anchors CIN as a pervasive upstream driver in EAC.
GEO:GSE316062 SUPPORT Human Clinical
"Coupling in situ CIN detection with single-nucleus RNA sequencing and multiplex immunophenotyping of human EAC, we link CIN to tumor-intrinsic innate immune activation, CXCL8 expression, and myeloid cell-mediated immunosuppression."
This directly supports a CIN-linked chemokine and myeloid immunosuppressive program in human EAC.
Adaptive Immune Resistance
A subset of Barrett-associated dysplastic and invasive esophageal adenocarcinoma lesions expresses PD-L1 pathway markers, consistent with an adaptive immune-resistance state that can be therapeutically targeted.
negative regulation of T cell mediated immunity link ↑ INCREASED
Downstream
T Cell Exhaustion and Immune Escape Chronic checkpoint signaling drives tumor-infiltrating T cells into an exhausted, non-productive state.
Show evidence (1 reference)
PMID:31724072 PARTIAL Human Clinical
"A higher prevalence of PD-L1-positive cases was observed among esophageal specimens compared with gastric ones (p = 0.0003), in high-grade and adenocarcinoma samples in comparison with low-grade dysplasia (p < 0.0001), and in lesions with mismatch repair deficiency (p = 0.028)."
This supports PD-L1 pathway activation across Barrett-associated dysplastic and adenocarcinoma lesions, although it does not by itself define the full immune state of all EACs.
T Cell Exhaustion and Immune Escape
In the immunosuppressive EAC microenvironment, chronically stimulated tumor-infiltrating T cells acquire an exhausted phenotype with impaired effector cytokine production and cytolytic activity, contributing to immune escape.
exhausted T cell link
exhausted T cell differentiation link ↑ INCREASED
Show evidence (1 reference)
PMID:26086965 SUPPORT Other
"The exhausted T cells in the tumor microenvironment show overexpressed inhibitory receptors, decreased effector cytokine production and cytolytic activity, leading to the failure of cancer elimination."
This review directly supports an exhausted intratumoral T-cell state as a mechanistic consequence of checkpoint-mediated immune escape.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Esophageal Adenocarcinoma Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

6
Blood 2
Gastrointestinal Hemorrhage Gastrointestinal hemorrhage (HP:0002239)
Show evidence (1 reference)
PMID:8012079 PARTIAL Human Clinical
"The patient, a 74-year-old man had the chief complaints of hematemesis and melena."
This case report supports upper gastrointestinal bleeding as a possible presentation of esophageal adenocarcinoma.
Anemia Anemia (HP:0001903)
Show evidence (1 reference)
PMID:25957861 SUPPORT Human Clinical
"EAC most commonly presents with dysphagia, but patients may also present with weight loss, anemia, or manifestations of distant metastases."
This supports anemia as a recognized clinical presentation of EAC.
Digestive 3
Dysphagia FREQUENT Dysphagia (HP:0002015)
Show evidence (1 reference)
PMID:25957861 SUPPORT Human Clinical
"EAC most commonly presents with dysphagia, but patients may also present with weight loss, anemia, or manifestations of distant metastases."
Author wording "most commonly presents with" supports dysphagia as a frequent phenotype.
Odynophagia Odynophagia (HP:0032043)
Show evidence (1 reference)
PMID:27214976 PARTIAL Human Clinical
"Oesophageal cancer commonly presents with dysphagia or odynophagia."
This mixed esophageal cancer review supports odynophagia as a clinically recognized presentation, although it is not specific to EAC.
Gastroesophageal Reflux Gastroesophageal reflux (HP:0002020)
Show evidence (1 reference)
PMID:25957861 PARTIAL Human Clinical
"Several other risk factors for this cancer have been described, including chronic heartburn, tobacco use, white race, and obesity."
The abstract frames chronic heartburn as a risk factor rather than a presenting symptom, but it supports frequent antecedent reflux symptoms in patients who develop EAC.
Growth 1
Weight Loss FREQUENT Weight loss (HP:0001824)
Show evidence (2 references)
PMID:25957861 SUPPORT Human Clinical
"EAC most commonly presents with dysphagia, but patients may also present with weight loss, anemia, or manifestations of distant metastases."
This supports weight loss as a recognized presentation feature of EAC.
PMID:40277743 PARTIAL Human Clinical
"Significant weight loss (>10%) was ubiquitously observed in 54% (n = 64) of patients, and this group had shorter OS (HR: 2.2; 95%CI: 1.2-4.1; p = 0.009)."
54% falls in the FREQUENT band, although this estimate comes from a mixed gastric, gastroesophageal junction, and esophageal adenocarcinoma surgical cohort rather than an EAC-only series.
🧬

Genetic Associations

4
TP53 (Somatic Loss-of-Function Mutation)
Show evidence (1 reference)
PMID:34503107 SUPPORT Human Clinical
"The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes."
This review identifies TP53 as the dominant recurrent genomic lesion in EAC.
ERBB2 (HER2) (Somatic Amplification)
Show evidence (1 reference)
PMID:21267790 SUPPORT Human Clinical
"True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression."
This defines a distinct ERBB2-amplified EAC subset that can be biomarker-stratified therapeutically.
CDKN2A (Recurrent Somatic Alteration)
Show evidence (1 reference)
PMID:34503107 SUPPORT Human Clinical
"The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes."
This supports CDKN2A as a recurrent somatic alteration in EAC.
SMAD4 (Recurrent Somatic Alteration)
Show evidence (1 reference)
PMID:34503107 SUPPORT Human Clinical
"The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes."
This supports SMAD4 as a recurrent somatic alteration in EAC.
💊

Treatments

4
Endoscopic Therapy for T1a Disease
Action: surgical procedure MAXO:0000004
T1a esophageal adenocarcinoma can be managed endoscopically in carefully staged patients, preserving the esophagus while treating superficial neoplasia.
Show evidence (1 reference)
PMID:25957861 SUPPORT Human Clinical
"T1a EAC may be treated endoscopically, and some patients with T1b disease may also benefit from endoscopic therapy."
This supports endoscopic therapy as a standard option for superficial T1a disease.
Esophagectomy
Action: surgical procedure MAXO:0000004
Esophagectomy remains a core treatment for resectable invasive disease and is often used for locally advanced tumors in combination with neoadjuvant therapy.
Show evidence (1 reference)
PMID:25957861 SUPPORT Human Clinical
"Locally advanced disease is generally managed with esophagectomy, often accompanied by neoadjuvant chemoradiotherapy or chemotherapy."
This supports esophagectomy as a central treatment modality for invasive EAC.
Neoadjuvant CROSS Chemoradiotherapy Plus Surgery
Action: chemotherapy MAXO:0000647
Agent: carboplatin ↗ paclitaxel ↗
For locally advanced resectable disease, carboplatin-paclitaxel based neoadjuvant chemoradiotherapy followed by surgery improves long-term survival.
Show evidence (1 reference)
PMID:33891478 SUPPORT Human Clinical
"Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer."
This supports the CROSS regimen as a standard neoadjuvant treatment platform for resectable locally advanced disease.
Adjuvant Nivolumab
Action: immunotherapy Ontology label: Immunotherapy NCIT:C15262
Agent: nivolumab ↗
In resected esophageal or gastroesophageal junction cancer with residual pathologic disease after neoadjuvant chemoradiotherapy, adjuvant nivolumab prolongs disease-free survival.
Mechanism Target:
Adaptive Immune Resistance
Show evidence (1 reference)
PMID:33789008 SUPPORT Human Clinical
"Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo."
This supports adjuvant PD-1 blockade after trimodality therapy in high-risk resected disease.
🔀

Differential Diagnoses

2

Conditions with similar clinical presentations that must be differentiated from Esophageal Adenocarcinoma:

Barrett esophagus Not Yet Curated MONDO:0013662
Overlapping Features Barrett esophagus is the key precursor lesion and a central diagnostic differential when evaluating glandular esophageal lesions that have not yet progressed to invasive adenocarcinoma.
Distinguishing Features
  • Barrett esophagus is a metaplastic precursor lesion, whereas EAC is invasive malignancy.
  • Barrett-associated dysplasia requires careful histologic separation from frankly invasive adenocarcinoma.
Show evidence (1 reference)
PMID:40874980 SUPPORT Human Clinical
"Barrett esophagus (BE) is the only known histological precursor to esophageal adenocarcinoma (EAC)."
This directly supports Barrett esophagus as the central precursor-state differential during EAC evaluation.
Esophageal squamous cell carcinoma MONDO:0005580
Overlapping Features ESCC is the main histologic differential diagnosis because it shares the same anatomic site as EAC but arises from squamous mucosa and has distinct environmental and molecular risk patterns.
Distinguishing Features
  • EAC usually arises in distal esophagus from Barrett metaplasia.
  • ESCC is more strongly linked to tobacco and alcohol exposure and squamous mucosal transformation.
Show evidence (1 reference)
PMID:20224883 SUPPORT Human Clinical
"Esophageal cancers are classified into two histological types; esophageal squamous cell carcinoma (ESCC), and adenocarcinoma"
This directly supports ESCC as the alternative major esophageal histology that must be distinguished from EAC.
📊

Related Datasets

2
Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS-chemokine-myeloid axis geo:GSE316127
Bulk RNA-seq dataset from engineered Barrett-derived models with graded chromosomal instability used to define CIN-linked chemokine signaling and immunosuppressive myeloid programs in esophageal adenocarcinoma.
human BULK RNA SEQ
Conditions: TP53/CDKN2A-altered CIN model control Barrett-derived epithelial model
Show evidence (1 reference)
GEO:GSE316127 SUPPORT In Vitro
"RNA-seq was performed on isogenic CP-A cell lines exhibiting distinct inherent levels of chromosomal instability (CIN)."
This directly supports the experimental design and relevance of the dataset for CIN-driven EAC biology.
Single-nucleus RNA sequencing of chromosomal-instability-linked immune states in esophageal adenocarcinoma geo:GSE316062
Single-nucleus RNA-seq companion dataset from human EAC used to connect chromosomal instability to innate immune activation and myeloid-dominated microenvironmental states.
human SINGLE CELL RNA SEQ
Conditions: human esophageal adenocarcinoma tumor CIN-high tumor microenvironment
🔬

Clinical Trials

2
NCT02743494 PHASE_III COMPLETED
Randomized phase III adjuvant nivolumab trial in resected esophageal or gastroesophageal junction cancer after neoadjuvant chemoradiotherapy.
Show evidence (1 reference)
clinicaltrials:NCT02743494 SUPPORT Human Clinical
"The primary purpose of this study is to determine whether Nivolumab will improve disease-free survival compared with placebo."
This directly supports a pivotal adjuvant immunotherapy trial relevant to resected EAC.
NCT03189719 PHASE_III COMPLETED
Phase III first-line pembrolizumab plus cisplatin and 5-FU trial in locally advanced or metastatic esophageal carcinoma, including adenocarcinoma.
Show evidence (1 reference)
clinicaltrials:NCT03189719 SUPPORT Human Clinical
"The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and 5-fluorouracil (5-FU) versus placebo plus SOC chemotherapy with cisplatin and 5-FU as first-line treatment in participants with locally advanced or metastatic..."
This supports active phase III evaluation of pembrolizumab-based first-line therapy in advanced esophageal carcinoma, including adenocarcinoma.
{ }

Source YAML

click to show 
name: Esophageal Adenocarcinoma
creation_date: "2026-04-12T04:03:44Z"
updated_date: "2026-04-21T13:35:41Z"
description: >-
  Esophageal adenocarcinoma (EAC) is a gland-forming malignancy of the
  esophagus that usually arises in the distal esophagus from Barrett metaplastic
  mucosa after chronic gastroesophageal reflux. It is characterized by late
  clinical presentation, frequent TP53 alteration, chromosomal instability, and
  recurrent copy-number changes that can create targetable oncogenic subsets
  such as ERBB2-amplified disease.
categories:
- Gastrointestinal Cancer
- Esophageal Cancer
- Adenocarcinoma
- Solid Tumor
parents:
- carcinoma of esophagus
- adenocarcinoma
has_subtypes:
- name: HER2-amplified
  display_name: HER2-amplified esophageal adenocarcinoma
  description: >-
    Molecular subset with ERBB2 amplification and HER2 overexpression that can
    be biomarker-selected for HER2-directed therapy.
  classification: molecular
  evidence:
  - reference: PMID:21267790
    reference_title: "Her-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression."
    explanation: This directly supports a clinically relevant ERBB2-amplified molecular subset in esophageal adenocarcinoma.
disease_term:
  preferred_term: esophageal adenocarcinoma
  term:
    id: MONDO:0005028
    label: esophageal adenocarcinoma
pathophysiology:
- name: GERD-Driven Esophageal Injury and Inflammation
  description: >-
    Chronic gastroesophageal reflux exposes the esophageal mucosa to refluxate,
    producing mucosal inflammation and injury that sets the stage for Barrett
    metaplasia and later adenocarcinoma.
  evidence:
  - reference: PMID:32119349
    reference_title: "Gastroesophageal Reflux Disease (GERD)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Gastroesophageal reflux disease (GERD) is a condition in which retrograde flow of stomach contents into the esophagus or beyond into other regions, eg, oral cavity, larynx, or the lungs, occurs, primarily resulting in inflammation of the esophageal mucosa."
    explanation: This supports reflux-driven mucosal injury and inflammation as the initiating upstream process.
  - reference: PMID:34503107
    reference_title: "Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Barrett's esophagus (BE), a metaplastic response of the esophagus to gastro-esophageal reflux disease, is the main risk factor for the development of EAC. Almost all EACs are derived from BE."
    explanation: This links chronic reflux to the metaplastic Barrett field that precedes EAC.
  cell_types:
  - preferred_term: epithelial cell of esophagus
    term:
      id: CL:0002252
      label: epithelial cell of esophagus
  locations:
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  downstream:
  - target: Barrett Esophagus Precursor State
    description: Persistent reflux injury promotes Barrett metaplasia.
- name: Barrett Esophagus Precursor State
  description: >-
    Barrett esophagus is the principal precursor lesion for esophageal
    adenocarcinoma and provides the metaplastic epithelial field from which most
    EAC develops.
  evidence:
  - reference: PMID:40874980
    reference_title: "Screening for Barrett Esophagus and Esophageal Adenocarcinoma: Approaches and Outcomes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Barrett esophagus (BE) is the only known histological precursor to esophageal adenocarcinoma (EAC)."
    explanation: This directly identifies Barrett esophagus as the precursor lesion to EAC.
  - reference: PMID:34503107
    reference_title: "Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Barrett's esophagus (BE), a metaplastic response of the esophagus to gastro-esophageal reflux disease, is the main risk factor for the development of EAC. Almost all EACs are derived from BE."
    explanation: This links chronic reflux-driven Barrett metaplasia to the origin of most EACs.
  cell_types:
  - preferred_term: epithelial cell of esophagus
    term:
      id: CL:0002252
      label: epithelial cell of esophagus
  locations:
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  downstream:
  - target: TP53 Somatic Mutation
    description: Barrett progression acquires tumor suppressor loss and increasingly unstable genomes.
- name: TP53 Somatic Mutation
  description: >-
    TP53 is the dominant recurrent tumor suppressor alteration in EAC and is
    commonly acquired during progression from Barrett dysplasia toward
    carcinoma.
  evidence:
  - reference: PMID:34503107
    reference_title: "Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes."
    explanation: This establishes TP53 mutation as the dominant recurrent genomic lesion in EAC.
  cell_types:
  - preferred_term: epithelial cell of esophagus
    term:
      id: CL:0002252
      label: epithelial cell of esophagus
  locations:
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  downstream:
  - target: Chromosomal Instability
    description: TP53 loss permits propagation of cell division errors as heritable chromosomal instability.
- name: Chromosomal Instability
  description: >-
    Following TP53 loss, Barrett progression acquires multigenerational
    chromosomal instability with whole-genome duplication and complex
    copy-number rearrangements.
  evidence:
  - reference: PMID:37794034
    reference_title: "Genomic signatures of past and present chromosomal instability in Barrett's esophagus and early esophageal adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We identify distinct patterns of copy-number evolution indicating multigenerational chromosomal instability that is initiated by cell division errors but propagated only after p53 loss."
    explanation: This supports ongoing chromosomal instability as a downstream consequence of p53 loss in Barrett progression and early EAC.
  cell_types:
  - preferred_term: epithelial cell of esophagus
    term:
      id: CL:0002252
      label: epithelial cell of esophagus
  biological_processes:
  - preferred_term: DNA damage response
    modifier: ABNORMAL
    term:
      id: GO:0006974
      label: DNA damage response
  locations:
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  downstream:
  - target: Copy-Number Driven Oncogenic Signaling
    description: Ongoing chromosomal instability generates amplifications and deletions that reinforce tumor growth signaling.
- name: Copy-Number Driven Oncogenic Signaling
  description: >-
    EAC carries a heavy burden of genomic rearrangements with amplifications and
    deletions, producing subsets with ERBB2 and other growth-pathway
    alterations that feed MAPK and PI3K-AKT signaling and tumor proliferation.
  evidence:
  - reference: PMID:34503107
    reference_title: "Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "EAC is characterized by a high burden of point mutations and genomic rearrangements, resulting in amplifications and deletions of genomic regions."
    explanation: This supports copy-number-driven oncogenic signaling as a core feature of EAC genomes.
  - reference: PMID:21267790
    reference_title: "Her-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression."
    explanation: This demonstrates a clinically relevant ERBB2-amplified subset within esophageal adenocarcinoma.
  biological_processes:
  - preferred_term: MAPK cascade
    modifier: INCREASED
    term:
      id: GO:0000165
      label: MAPK cascade
  - preferred_term: phosphatidylinositol 3-kinase signaling
    modifier: INCREASED
    term:
      id: GO:0043491
      label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  locations:
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  downstream:
  - target: Chromosomal Instability-Linked Innate Immune and Myeloid Signaling
    description: Ongoing copy-number instability drives cGAS-linked inflammatory chemokine programs.
- name: Chromosomal Instability-Linked Innate Immune and Myeloid Signaling
  description: >-
    In chromosomally unstable EAC, innate immune sensing and chemokine signaling
    can recruit myeloid suppressor populations and create an immunosuppressive
    microenvironment.
  cell_types:
  - preferred_term: myeloid cell
    term:
      id: CL:0000763
      label: myeloid cell
  biological_processes:
  - preferred_term: innate immune response
    modifier: INCREASED
    term:
      id: GO:0045087
      label: innate immune response
  - preferred_term: chemokine production
    modifier: INCREASED
    term:
      id: GO:0032602
      label: chemokine production
  evidence:
  - reference: GEO:GSE316127
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "Chromosomal instability (CIN), a pervasive feature of esophageal adenocarcinoma (EAC), drives tumor aggressiveness and metastasis."
    explanation: This GEO-linked study anchors CIN as a pervasive upstream driver in EAC.
  - reference: GEO:GSE316062
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Coupling in situ CIN detection with single-nucleus RNA sequencing and multiplex immunophenotyping of human EAC, we link CIN to tumor-intrinsic innate immune activation, CXCL8 expression, and myeloid cell-mediated immunosuppression."
    explanation: This directly supports a CIN-linked chemokine and myeloid immunosuppressive program in human EAC.
  downstream:
  - target: Adaptive Immune Resistance
    description: Myeloid-dominated inflammatory signaling reinforces checkpoint-mediated immune escape.
- name: Adaptive Immune Resistance
  conforms_to: "immune_checkpoint_blockade#Adaptive Immune Resistance"
  description: >-
    A subset of Barrett-associated dysplastic and invasive esophageal
    adenocarcinoma lesions expresses PD-L1 pathway markers, consistent with an
    adaptive immune-resistance state that can be therapeutically targeted.
  biological_processes:
  - preferred_term: negative regulation of T cell mediated immunity
    modifier: INCREASED
    term:
      id: GO:0002710
      label: negative regulation of T cell mediated immunity
  evidence:
  - reference: PMID:31724072
    reference_title: "PD-L1 expression in gastroesophageal dysplastic lesions."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "A higher prevalence of PD-L1-positive cases was observed among esophageal specimens compared with gastric ones (p = 0.0003), in high-grade and adenocarcinoma samples in comparison with low-grade dysplasia (p < 0.0001), and in lesions with mismatch repair deficiency (p = 0.028)."
    explanation: This supports PD-L1 pathway activation across Barrett-associated dysplastic and adenocarcinoma lesions, although it does not by itself define the full immune state of all EACs.
  downstream:
  - target: T Cell Exhaustion and Immune Escape
    description: Chronic checkpoint signaling drives tumor-infiltrating T cells into an exhausted, non-productive state.
- name: T Cell Exhaustion and Immune Escape
  conforms_to: "immune_checkpoint_blockade#T Cell Exhaustion and Immune Escape"
  description: >-
    In the immunosuppressive EAC microenvironment, chronically stimulated
    tumor-infiltrating T cells acquire an exhausted phenotype with impaired
    effector cytokine production and cytolytic activity, contributing to immune
    escape.
  cell_types:
  - preferred_term: exhausted T cell
    term:
      id: CL:0011025
      label: exhausted T cell
  biological_processes:
  - preferred_term: exhausted T cell differentiation
    modifier: INCREASED
    term:
      id: GO:0160083
      label: exhausted T cell differentiation
  evidence:
  - reference: PMID:26086965
    reference_title: "T-cell exhaustion in the tumor microenvironment."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The exhausted T cells in the tumor microenvironment show overexpressed inhibitory receptors, decreased effector cytokine production and cytolytic activity, leading to the failure of cancer elimination."
    explanation: This review directly supports an exhausted intratumoral T-cell state as a mechanistic consequence of checkpoint-mediated immune escape.
phenotypes:
- name: Dysphagia
  category: Gastrointestinal
  frequency: FREQUENT
  description: >-
    Progressive swallowing difficulty is the most common presenting symptom and
    often reflects locally advanced luminal disease.
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:25957861
    reference_title: "Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "EAC most commonly presents with dysphagia, but patients may also present with weight loss, anemia, or manifestations of distant metastases."
    explanation: Author wording "most commonly presents with" supports dysphagia as a frequent phenotype.
- name: Odynophagia
  category: Gastrointestinal
  description: >-
    Painful swallowing can occur as the tumor narrows and inflames the
    esophageal lumen, usually late in the disease course.
  phenotype_term:
    preferred_term: Odynophagia
    term:
      id: HP:0032043
      label: Odynophagia
  evidence:
  - reference: PMID:27214976
    reference_title: "Early diagnosis of oesophageal cancer improves outcomes."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Oesophageal cancer commonly presents with dysphagia or odynophagia."
    explanation: This mixed esophageal cancer review supports odynophagia as a clinically recognized presentation, although it is not specific to EAC.
- name: Gastroesophageal Reflux
  category: Gastrointestinal
  description: >-
    Chronic reflux symptoms often precede EAC and are part of the clinical
    syndrome in many patients who progress through Barrett metaplasia.
  phenotype_term:
    preferred_term: Gastroesophageal reflux
    term:
      id: HP:0002020
      label: Gastroesophageal reflux
  evidence:
  - reference: PMID:25957861
    reference_title: "Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Several other risk factors for this cancer have been described, including chronic heartburn, tobacco use, white race, and obesity."
    explanation: The abstract frames chronic heartburn as a risk factor rather than a presenting symptom, but it supports frequent antecedent reflux symptoms in patients who develop EAC.
- name: Weight Loss
  category: Constitutional
  frequency: FREQUENT
  description: >-
    Weight loss is common at presentation and during curative therapy because of
    impaired oral intake, catabolic burden, and treatment intensity.
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: PMID:25957861
    reference_title: "Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "EAC most commonly presents with dysphagia, but patients may also present with weight loss, anemia, or manifestations of distant metastases."
    explanation: This supports weight loss as a recognized presentation feature of EAC.
  - reference: PMID:40277743
    reference_title: "The Impact of Peri-Operative Nutritional Status on Survival in Gastroesophageal Adenocarcinoma."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "Significant weight loss (>10%) was ubiquitously observed in 54% (n = 64) of patients, and this group had shorter OS (HR: 2.2; 95%CI: 1.2-4.1; p = 0.009)."
    explanation: 54% falls in the FREQUENT band, although this estimate comes from a mixed gastric, gastroesophageal junction, and esophageal adenocarcinoma surgical cohort rather than an EAC-only series.
- name: Gastrointestinal Hemorrhage
  category: Gastrointestinal
  description: >-
    Some tumors present with overt upper gastrointestinal bleeding such as
    hematemesis or melena.
  phenotype_term:
    preferred_term: Gastrointestinal hemorrhage
    term:
      id: HP:0002239
      label: Gastrointestinal hemorrhage
  evidence:
  - reference: PMID:8012079
    reference_title: "Superficial and protruding type of esophageal adenocarcinoma mucocellulare and muconodulare confined mostly to the lamina propria mucosa and partly in the submucosal layer."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient, a 74-year-old man had the chief complaints of hematemesis and melena."
    explanation: This case report supports upper gastrointestinal bleeding as a possible presentation of esophageal adenocarcinoma.
- name: Anemia
  category: Hematologic
  description: >-
    Anemia may accompany tumor-associated bleeding, nutritional compromise, or
    advanced disease.
  phenotype_term:
    preferred_term: Anemia
    term:
      id: HP:0001903
      label: Anemia
  evidence:
  - reference: PMID:25957861
    reference_title: "Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "EAC most commonly presents with dysphagia, but patients may also present with weight loss, anemia, or manifestations of distant metastases."
    explanation: This supports anemia as a recognized clinical presentation of EAC.
diagnosis:
- name: Upper endoscopy with biopsy
  description: >-
    Diagnostic evaluation of esophageal adenocarcinoma begins with upper
    endoscopy and tissue biopsy for histologic confirmation.
  diagnosis_term:
    preferred_term: endoscopic procedure
    term:
      id: MAXO:0000130
      label: endoscopic procedure
  evidence:
  - reference: PMID:25957861
    reference_title: "Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cross-sectional imaging analysis, such as with computed tomography (CT), does not accurately identify localized EAC. Barium esophagrams can identify irregular strictures or masses, but upper endoscopy with biopsy collection and histologic analysis is the standard for diagnosis."
    explanation: This directly supports upper endoscopy with biopsy as the diagnostic standard.
- name: Endoscopic ultrasonography
  description: >-
    Endoscopic ultrasonography helps define local tumor extent and regional nodal
    involvement after histologic diagnosis.
  diagnosis_term:
    preferred_term: endoscopic procedure
    term:
      id: MAXO:0000130
      label: endoscopic procedure
  evidence:
  - reference: PMID:25957861
    reference_title: "Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Endoscopic ultrasonography is useful to assess the local extent of disease as well as the involvement of regional lymph nodes."
    explanation: This directly supports endoscopic ultrasonography as a staging procedure in EAC.
differential_diagnoses:
- name: Barrett esophagus
  disease_term:
    preferred_term: Barrett esophagus
    term:
      id: MONDO:0013662
      label: Barrett esophagus
  description: >-
    Barrett esophagus is the key precursor lesion and a central diagnostic
    differential when evaluating glandular esophageal lesions that have not yet
    progressed to invasive adenocarcinoma.
  distinguishing_features:
  - Barrett esophagus is a metaplastic precursor lesion, whereas EAC is invasive malignancy.
  - Barrett-associated dysplasia requires careful histologic separation from frankly invasive adenocarcinoma.
  evidence:
  - reference: PMID:40874980
    reference_title: "Screening for Barrett Esophagus and Esophageal Adenocarcinoma: Approaches and Outcomes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Barrett esophagus (BE) is the only known histological precursor to esophageal adenocarcinoma (EAC)."
    explanation: This directly supports Barrett esophagus as the central precursor-state differential during EAC evaluation.
- name: Esophageal squamous cell carcinoma
  disease_term:
    preferred_term: esophageal squamous cell carcinoma
    term:
      id: MONDO:0005580
      label: esophageal squamous cell carcinoma
  description: >-
    ESCC is the main histologic differential diagnosis because it shares the
    same anatomic site as EAC but arises from squamous mucosa and has distinct
    environmental and molecular risk patterns.
  distinguishing_features:
  - EAC usually arises in distal esophagus from Barrett metaplasia.
  - ESCC is more strongly linked to tobacco and alcohol exposure and squamous mucosal transformation.
  evidence:
  - reference: PMID:20224883
    reference_title: "Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: molecular mechanisms of carcinogenesis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Esophageal cancers are classified into two histological types; esophageal squamous cell carcinoma (ESCC), and adenocarcinoma"
    explanation: This directly supports ESCC as the alternative major esophageal histology that must be distinguished from EAC.
genetic:
- name: TP53
  gene_term:
    preferred_term: TP53
    term:
      id: hgnc:11998
      label: TP53
  association: Somatic Loss-of-Function Mutation
  evidence:
  - reference: PMID:34503107
    reference_title: "Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes."
    explanation: This review identifies TP53 as the dominant recurrent genomic lesion in EAC.
  notes: >-
    TP53 alteration is the defining recurrent tumor suppressor event in EAC and
    is closely tied to chromosomal instability during progression from Barrett
    dysplasia to carcinoma.
- name: ERBB2 (HER2)
  gene_term:
    preferred_term: ERBB2
    term:
      id: hgnc:3430
      label: ERBB2
  association: Somatic Amplification
  evidence:
  - reference: PMID:21267790
    reference_title: "Her-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "True HER2 gene amplification was detected in 14 esophageal cancer specimens (16%), and 92% of those with high-level HER2 amplification showed positive HER2 protein overexpression."
    explanation: This defines a distinct ERBB2-amplified EAC subset that can be biomarker-stratified therapeutically.
  notes: >-
    ERBB2 amplification identifies a clinically relevant subset of EAC with
    receptor tyrosine kinase pathway activation and potential eligibility for
    HER2-directed therapy.
- name: CDKN2A
  gene_term:
    preferred_term: CDKN2A
    term:
      id: hgnc:1787
      label: CDKN2A
  association: Recurrent Somatic Alteration
  evidence:
  - reference: PMID:34503107
    reference_title: "Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes."
    explanation: This supports CDKN2A as a recurrent somatic alteration in EAC.
  notes: >-
    CDKN2A is one of the recurrent genomic alterations that follows TP53 loss in
    EAC and contributes to dysregulated cell-cycle control.
- name: SMAD4
  gene_term:
    preferred_term: SMAD4
    term:
      id: hgnc:6770
      label: SMAD4
  association: Recurrent Somatic Alteration
  evidence:
  - reference: PMID:34503107
    reference_title: "Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The tumor suppressor gene TP53 is mutated in 70 to 80% of tumors followed by genomic alterations in CDKN2A, KRAS, ERBB2, ARID1A, SMAD4 and a long tail of less frequently mutated genes."
    explanation: This supports SMAD4 as a recurrent somatic alteration in EAC.
  notes: >-
    SMAD4 loss contributes to impaired TGF-beta tumor suppressive signaling in a
    subset of EACs.
treatments:
- name: Endoscopic Therapy for T1a Disease
  description: >-
    T1a esophageal adenocarcinoma can be managed endoscopically in carefully
    staged patients, preserving the esophagus while treating superficial
    neoplasia.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  evidence:
  - reference: PMID:25957861
    reference_title: "Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "T1a EAC may be treated endoscopically, and some patients with T1b disease may also benefit from endoscopic therapy."
    explanation: This supports endoscopic therapy as a standard option for superficial T1a disease.
- name: Esophagectomy
  description: >-
    Esophagectomy remains a core treatment for resectable invasive disease and
    is often used for locally advanced tumors in combination with neoadjuvant
    therapy.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  evidence:
  - reference: PMID:25957861
    reference_title: "Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Locally advanced disease is generally managed with esophagectomy, often accompanied by neoadjuvant chemoradiotherapy or chemotherapy."
    explanation: This supports esophagectomy as a central treatment modality for invasive EAC.
- name: Neoadjuvant CROSS Chemoradiotherapy Plus Surgery
  description: >-
    For locally advanced resectable disease, carboplatin-paclitaxel based
    neoadjuvant chemoradiotherapy followed by surgery improves long-term
    survival.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: MAXO:0000647
      label: chemotherapy
    therapeutic_agent:
    - preferred_term: carboplatin
      term:
        id: CHEBI:31355
        label: carboplatin
    - preferred_term: paclitaxel
      term:
        id: CHEBI:45863
        label: paclitaxel
  evidence:
  - reference: PMID:33891478
    reference_title: "Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer."
    explanation: This supports the CROSS regimen as a standard neoadjuvant treatment platform for resectable locally advanced disease.
- name: Adjuvant Nivolumab
  description: >-
    In resected esophageal or gastroesophageal junction cancer with residual
    pathologic disease after neoadjuvant chemoradiotherapy, adjuvant nivolumab
    prolongs disease-free survival.
  treatment_term:
    preferred_term: immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
    therapeutic_agent:
    - preferred_term: nivolumab
      term:
        id: NCIT:C68814
        label: Nivolumab
  target_mechanisms:
  - target: Adaptive Immune Resistance
  evidence:
  - reference: PMID:33789008
    reference_title: "Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo."
    explanation: This supports adjuvant PD-1 blockade after trimodality therapy in high-risk resected disease.
clinical_trials:
- name: NCT02743494
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Randomized phase III adjuvant nivolumab trial in resected esophageal or
    gastroesophageal junction cancer after neoadjuvant chemoradiotherapy.
  evidence:
  - reference: clinicaltrials:NCT02743494
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The primary purpose of this study is to determine whether Nivolumab will improve disease-free survival compared with placebo.
    explanation: This directly supports a pivotal adjuvant immunotherapy trial relevant to resected EAC.
- name: NCT03189719
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Phase III first-line pembrolizumab plus cisplatin and 5-FU trial in locally
    advanced or metastatic esophageal carcinoma, including adenocarcinoma.
  evidence:
  - reference: clinicaltrials:NCT03189719
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and 5-fluorouracil (5-FU) versus placebo plus SOC chemotherapy with cisplatin and 5-FU as first-line treatment in participants with locally advanced or metastatic esophageal carcinoma.
    explanation: This supports active phase III evaluation of pembrolizumab-based first-line therapy in advanced esophageal carcinoma, including adenocarcinoma.
datasets:
- accession: geo:GSE316127
  title: Chromosomal instability shapes the tumor microenvironment of esophageal adenocarcinoma via a cGAS-chemokine-myeloid axis
  description: >-
    Bulk RNA-seq dataset from engineered Barrett-derived models with graded
    chromosomal instability used to define CIN-linked chemokine signaling and
    immunosuppressive myeloid programs in esophageal adenocarcinoma.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  conditions:
  - TP53/CDKN2A-altered CIN model
  - control Barrett-derived epithelial model
  evidence:
  - reference: GEO:GSE316127
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "RNA-seq was performed on isogenic CP-A cell lines exhibiting distinct inherent levels of chromosomal instability (CIN)."
    explanation: This directly supports the experimental design and relevance of the dataset for CIN-driven EAC biology.
- accession: geo:GSE316062
  title: Single-nucleus RNA sequencing of chromosomal-instability-linked immune states in esophageal adenocarcinoma
  description: >-
    Single-nucleus RNA-seq companion dataset from human EAC used to connect
    chromosomal instability to innate immune activation and myeloid-dominated
    microenvironmental states.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  conditions:
  - human esophageal adenocarcinoma tumor
  - CIN-high tumor microenvironment
classifications:
  icdo_morphology:
    classification_value: Adenocarcinoma
  harrisons_chapter:
  - classification_value: cancer
  - classification_value: solid tumor
references:
- reference: PMID:8012079
  title: Superficial and protruding type of esophageal adenocarcinoma mucocellulare and muconodulare confined mostly to the lamina propria mucosa and partly in the submucosal layer.
  findings: []
- reference: PMID:21267790
  title: Her-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival.
  findings: []
- reference: PMID:25957861
  title: Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma.
  findings: []
- reference: PMID:27214976
  title: Early diagnosis of oesophageal cancer improves outcomes.
  findings: []
- reference: PMID:32119349
  title: Gastroesophageal Reflux Disease (GERD).
  findings: []
- reference: PMID:33789008
  title: Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.
  findings: []
- reference: PMID:33891478
  title: 'Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial.'
  findings: []
- reference: PMID:34503107
  title: Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma.
  findings: []
- reference: PMID:37794034
  title: "Genomic signatures of past and present chromosomal instability in Barrett's esophagus and early esophageal adenocarcinoma."
  findings: []
- reference: PMID:40277743
  title: The Impact of Peri-Operative Nutritional Status on Survival in Gastroesophageal Adenocarcinoma.
  findings: []
- reference: PMID:40874980
  title: "Screening for Barrett Esophagus and Esophageal Adenocarcinoma: Approaches and Outcomes."
  findings: []
- reference: PMID:31724072
  title: PD-L1 expression in gastroesophageal dysplastic lesions.
  findings: []
📚

References & Deep Research

References

12
PMID:8012079
Superficial and protruding type of esophageal adenocarcinoma mucocellulare and muconodulare confined mostly to the lamina propria mucosa and partly in the submucosal layer.
No top-level findings curated for this source.
PMID:21267790
Her-2/neu gene amplification in esophageal adenocarcinoma and its influence on survival.
No top-level findings curated for this source.
PMID:25957861
Epidemiology, Diagnosis, and Management of Esophageal Adenocarcinoma.
No top-level findings curated for this source.
PMID:27214976
Early diagnosis of oesophageal cancer improves outcomes.
No top-level findings curated for this source.
PMID:32119349
Gastroesophageal Reflux Disease (GERD).
No top-level findings curated for this source.
PMID:33789008
Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.
No top-level findings curated for this source.
PMID:33891478
Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial.
No top-level findings curated for this source.
PMID:34503107
Genomic and Transcriptomic Characteristics of Esophageal Adenocarcinoma.
No top-level findings curated for this source.
PMID:37794034
Genomic signatures of past and present chromosomal instability in Barrett's esophagus and early esophageal adenocarcinoma.
No top-level findings curated for this source.
PMID:40277743
The Impact of Peri-Operative Nutritional Status on Survival in Gastroesophageal Adenocarcinoma.
No top-level findings curated for this source.
PMID:40874980
Screening for Barrett Esophagus and Esophageal Adenocarcinoma: Approaches and Outcomes.
No top-level findings curated for this source.
PMID:31724072
PD-L1 expression in gastroesophageal dysplastic lesions.
No top-level findings curated for this source.

Deep Research

1
Asta ▸
Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Esophageal Adenocarcinoma. Core disease mechanisms, molecular and cellular...
Asta Scientific Corpus Retrieval 20 citations 2026-04-21T08:23:40.819635

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Esophageal Adenocarcinoma. Core disease mechanisms, molecular and cellular...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 20
  • Snippets retrieved: 20

Relevant Papers

[1] The Oxidative Damage and Inflammation Mechanisms in GERD-Induced Barrett’s Esophagus

  • Authors: Deqiang Han, Chao Zhang
  • Year: 2022
  • Venue: Frontiers in Cell and Developmental Biology
  • URL: https://www.semanticscholar.org/paper/52a7eec845be5eb54ff56d0cd6699fabd843c502
  • DOI: 10.3389/fcell.2022.885537
  • PMID: 35721515
  • PMCID: 9199966
  • Citations: 24
  • Influential citations: 2
  • Summary: This review will discuss the mechanisms of Barrett’s metaplasia and adenocarcinoma underlying oxidative DNA damage in gastro-esophageal reflux disease patients based on recent clinical and basic findings.
  • Evidence snippets:
  • Snippet 1 (score: 0.502) > Barrett’s esophagus is a major complication of gastro-esophageal reflux disease and an important precursor lesion for the development of Barrett’s metaplasia and esophageal adenocarcinoma. However, the cellular and molecular mechanisms of Barrett’s metaplasia remain unclear. Inflammation-associated oxidative DNA damage could contribute to Barrett’s esophagus. It has been demonstrated that poly(ADP-ribose) polymerases (PARPs)-associated with ADP-ribosylation plays an important role in DNA damage and inflammatory response. A previous study indicated that there is inflammatory infiltration and oxidative DNA damage in the lower esophagus due to acid/bile reflux, and gastric acid could induce DNA damage in culture esophageal cells. This review will discuss the mechanisms of Barrett’s metaplasia and adenocarcinoma underlying oxidative DNA damage in gastro-esophageal reflux disease patients based on recent clinical and basic findings.

[2] Untargeted serum metabolomics reveals potential biomarkers and metabolic pathways associated with esophageal cancer

  • Authors: Xiao-Li Yang, Peng Wang, H. Ye, Ming Jiang, Yu Su et al.
  • Year: 2022
  • Venue: Frontiers in Oncology
  • URL: https://www.semanticscholar.org/paper/25d767023ab3c38a77d9801477447e11ddeb25ee
  • DOI: 10.3389/fonc.2022.938234
  • PMID: 36176418
  • PMCID: 9513043
  • Citations: 11
  • Summary: Comparative metabolomics showed that most metabolic differences were determined between the early stage (0–II) and the late stage (III and IV) among the 0–IV stages of esophageal cancer and between patients who received treatment and those who did not receive treatment.
  • Evidence snippets:
  • Snippet 1 (score: 0.502) > Esophageal cancer is a common malignant gastrointestinal tumor that ranks seventh and sixth in global cancer incidence and mortality, respectively. The cancer is known for typical geographic distribution in incidence and poor prognosis (1,2). According to the data released by the International Agency for Research on Cancer (IARC), there were 604,100 new cases of esophageal cancer and 544,076 deaths due to the disease worldwide in 2020, with China accounting for 53.7% and 55.4%, respectively (3). Notably, it is predicted that the incidence and mortality of esophageal cancer will rise yearly owing to the increasing aging of the population, posing a major challenge for health practitioners and a huge threat to human health (4). Thus, understanding the pathogenesis of esophageal cancer is helpful to identify new biomarkers for disease progression judgment and treatment prognosis. > Esophageal cancer is generally divided into two subtypes, namely, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC); most esophageal cancers are ESCC. ESCC carcinogenesis is related to external and internal factors and, thus, is a multifactorial disease. External factors include tobacco, alcohol, and behavior at high temperature (5)(6)(7), while internal factors are attributed to molecular events. However, the precise molecular events underlying ESCC etiology are only partially understood and thereby the detailed mechanism of occurrence and progression of ESCC has not been holistically revealed yet (8,9). These cause limited targeted therapies and insufficient clinical management in ESCC patients. Therefore, further understanding the pathogenesis of esophageal cancer and identifying diagnosis biomarkers can markedly improve the prognosis and therapy of patients with esophageal cancer. > Recently developed metabolomics provides an efficient approach to achieve a global assessment and validation of endogenous small-molecule metabolites within a cell or biologic system including cancer samples (10,11). Metabolomics is a key tool for biomarker discovery and personalized medicine including cancers (12,13).

[3] Network and pathway-based analysis of candidate genes associated with esophageal adenocarcinoma

  • Authors: Jun Yu Li, Ling-Yun Peng, Hanbing Li, Yan Cai, Peng Yao et al.
  • Year: 2023
  • Venue: Journal of Gastrointestinal Oncology
  • URL: https://www.semanticscholar.org/paper/cd129b2b5244c14d28008349621d9913dee4c9f1
  • DOI: 10.21037/jgo-22-1286
  • PMID: 36915458
  • PMCID: 10007923
  • Citations: 2
  • Summary: By integrating pathways and networks to explore the pathogenetic mechanisms underlying EA, the results could significantly improve the understanding of the molecular mechanisms of EA and form a basis for selection of potential molecular targets for further exploration.
  • Evidence snippets:
  • Snippet 1 (score: 0.498) > Background Previous studies have made some headway in analyzing esophageal adenocarcinoma (EA) with respect to pathogenic factors, treatment methods, and prognosis. However, far less is known about the molecular mechanisms. Thus, a comprehensive analysis focusing on the biological function and interaction of EA genes would provide valuable information for understanding the pathogenesis of EA, which may provide new insights into gene function as well as potential therapy targets. Methods We selected 109 genes related to EA by reviewing 458 publications from the PubMed database. In addition, performing gene enrichment assays, pathway enrichment assays, pathway crosstalk analysis, and extraction of EA-specific subnetwork were used to describe the relevant biochemical processes. Results Function analysis revealed that biological processes and biochemical pathways associated with apoptotic and metabolic processes, a variety of cancers, and drug reaction pathways. Further, 12 novel genes (PTHLH, SUMO2, TYMS, APP, PTGIR, SP1, UBC, COL1A1, GSTO1, TRAF6, BMP7, and RAB40B) were identified in the EA-specific network, which might provide helpful information for clinical application. Conclusions Overall, by integrating pathways and networks to explore the pathogenetic mechanisms underlying EA, our results could significantly improve our understanding of the molecular mechanisms of EA and form a basis for selection of potential molecular targets for further exploration.

[4] Current research progress in the role of reactive oxygen species in esophageal adenocarcinoma

  • Authors: Youzhen Hu, Xiaojun Ye, Ruihua Wang, Karen Poon
  • Year: 2021
  • Venue: Translational Cancer Research
  • URL: https://www.semanticscholar.org/paper/8dbcda573c59a95e84e8814e7cdc8f36c10034b4
  • DOI: 10.21037/tcr-19-1985
  • PMID: 35116481
  • PMCID: 8798363
  • Citations: 4
  • Summary: Current research progress on ROS and stemness activity, regulation of ROS by stanniocalcin-1/uncoupling protein 2 (UCP2), and inspiration for ROS in esophageal adenocarcinoma are summarized to guide further research and provide insight into the clinical treatment of esophagesis.
  • Evidence snippets:
  • Snippet 1 (score: 0.490) > In the past few decades, the incidence of esophageal adenocarcinoma has increased by six-fold in western countries, as the proton pump inhibitor targeting the gastric acid reflux has failed to control the disease. It is currently suggested that deoxycholic acid reflux leads to esophageal adenocarcinoma. As an inflammation-related cancer, the formation and progression of esophageal adenocarcinoma are closely related to the concentration of reactive oxygen species (ROS). Meanwhile, the critical developmental stage of esophageal adenocarcinoma involves characteristic pathological changes in which the distal esophageal squamous epithelial cells are replaced by intestinal columnar epithelial cells, suggesting the involvement of cancer stem cells. Thus, esophageal adenocarcinoma is a good model to study the interplay between ROS and stem cells in cancer. Until now, some important questions related to ROS in esophageal adenocarcinoma remain unanswered. For example, the molecular mechanism by which deoxycholic acid induces malignant transformation in esophageal adenocarcinoma remains unclear. In addition, whether ROS are involved in the induction of cancer stem cell formation by chemotherapeutic drugs and deoxycholic acid stimulation in esophageal adenocarcinoma remains to be further explored. This review summarizes current research progress on ROS and stemness activity, regulation of ROS by stanniocalcin-1 (STC1)/uncoupling protein 2 (UCP2), and inspiration for ROS in esophageal adenocarcinoma to guide further research and provide insight into the clinical treatment of esophageal adenocarcinoma.

[5] Bioinformatic Analysis of Prognostic Value and Immune Cell Infiltration of Chromobox Family Proteins in Esophageal Cancer

  • Authors: liangjiang xia, Wei Jiang, L. Pan, Jing-yi Yuan, Yu Feng et al.
  • Year: 2021
  • Venue: Unknown venue
  • URL: https://www.semanticscholar.org/paper/bfab38c20a3f41d695f3cbbe7937cc7fd745f99e
  • DOI: 10.21203/RS.3.RS-475438/V1
  • Summary: This study may provide new ideas for the selection of prognostic biomarkers in the CBXs in ESCA by identifying those that are correlated with patients’ individual cancer stages and the nodal metastatic status.
  • Evidence snippets:
  • Snippet 1 (score: 0.465) > Esophageal cancer has always been a major malignant tumor that threatens human health, and its incidence and mortality are the seventh and sixth of all malignant tumors, respectively 1 . Esophageal cancer is mainly divided into two histological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). As a highly aggressive malignant tumor, esophageal cancer is often accompanied by extensive lymph node metastasis, leading to a poor prognosis for patients. Although new treatments for esophageal cancer are emerging,and the molecular mechanism of esophageal cancer has been extensively studied, patient survival rate still needs to be improved 2 . With the research on the development mechanism of esophageal cancer, more prognostic biomarkers will be discovered to guide clinical work and bene t patients. DNA fragments, non-coding RNA, proteins, enzymes, hormones and metabolites can all be used as biomarkers. Hence, exploiting biomarkers with greater potential for prognosis and potential therapeutic targets of ESCA is an emergence. Chromobox (CBX) family proteins (CBXs) are currently divided into two categories: the polycomb (includes CBX2, CBX4, CBX6, CBX7, and CBX8) and heterochromatin protein 1 (includes CBX1, CBX3 and CBX5) 3,4 . Moreover, eight members of the CBX protein family are all involved in various biological processes, such as transcriptional repression, cell cycle regulation, lineage-commitment, tumor initiation, progression, development, and chromatin 5 . Abnormal expression of CBX family genes is related to the occurrence and development of various cancers, such as ESCC 6,7 ,breast cancer 8 , lung adenocarcinoma 9 , renal cell carcinoma 10 , cervical cancer 11 , bladder Cancer 12 , and colorectal cancer 13 . > Investigators reported that CBX3 and CBX8 had essential functions in ESCC 6,7 .CBX3 can promote the self-renewal of ESCC stem cells by inhibiting the activation of the P53/P21 pathway 7 .

[6] Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix

  • Authors: A. Palumbo, N. Meireles Da Costa, Bruno Pontes, Felipe Leite de Oliveira, Matheus Lohan Codeço et al.
  • Year: 2020
  • Venue: Cells
  • URL: https://www.semanticscholar.org/paper/b5fff733540f6d16dccbddf4be8d9cc0dd633c53
  • DOI: 10.3390/cells9020455
  • PMID: 32079295
  • PMCID: 7072790
  • Citations: 50
  • Influential citations: 2
  • Summary: The growing body of evidence on ECM’s role along esophageal carcinogenesis might provide a solid base to improve its management in the future and, due to the scarce knowledge on the cellular and molecular mechanisms involved in EC development, the wide spectrum of interactions potentially mediated by ECM may represent a singular intervention scenario in esophagesia carcinogenesis natural history.
  • Evidence snippets:
  • Snippet 1 (score: 0.459) > This lethal tumor confers a 5-year survival rate of about 15-25% of patients, demonstrating its poor prognosis [17]. There are two main EC histopathological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), which widely differ considering populations affected, etiological factors, and molecular alterations, among others. Although ESCC development is highly associated with tobacco and alcohol abuse and ingestion of high temperature beverages, for EAC, the main associated risk factors are obesity, gastroesophageal reflux disease (GERD), and Barrett's esophagus (BE), an intestinal metaplasia where the normal stratified squamous esophageal epithelium is replaced by a columnar intestinal-like one [18,19]. ESCC represents the predominant EC histotype; nevertheless, along with the increase in obesity rates in some western countries, the incidence of EAC has increased sharply over the past few decades [20,21]. Although EC is a remarkably incident and lethal cancer, the knowledge on its biology is still scarce. EC poor prognosis is directly associated with its late detection, which is a consequence of the lack of clinical symptoms in early tumor stages. Thus, the deeper understanding of the mechanisms involved in its genesis and/or progression may be useful in identifying potential markers for diagnosis and prognosis, as well as potential therapeutic targets. Therefore, the reciprocal interactions that occur between the cells and the surrounding ECM orchestrate a complex cascade of events during esophageal malignant transformation, where the adhesion mediated by glycoproteins and proteoglycans triggers signaling pathways, which induce the expression and activation of catalytic enzymes that, in turn, promote structural alterations in ECM stiffness and remodeling [15]. These alterations culminate in the activation of signaling pathways in a feedback loop mechanism (Figure 1). In this context, the interactions between EC and ECM may shed some light on the cellular and molecular mechanisms that govern the malignant development of these tumors.

[7] Malignant epithelia cells-derived spermine induces APOE+ macrophages to suppress tumor immunity in adenocarcinoma of the esophagogastric junction

  • Authors: Yan Zhang, Zhaoyang Liu, Huihui Sun, Zhenxiang Wang, Ye Chen et al.
  • Year: 2025
  • Venue: Frontiers in Medicine
  • URL: https://www.semanticscholar.org/paper/0e44617be42f8d481a707fcb529e3f1182f0a0f1
  • DOI: 10.3389/fmed.2025.1636699
  • PMID: 40963562
  • PMCID: 12436273
  • Citations: 1
  • Summary: This study identified AEG-like malignant cells as a high-risk subtype, revealed the metabolic-immune crosstalk driven by the spermine-STAT3-APOE axis in AEG progression, and provided potential targets for AEG metabolic intervention and immunotherapy.
  • Evidence snippets:
  • Snippet 1 (score: 0.439) > Adenocarcinoma of the esophagogastric junction (AEG) is a clinically challenging malignancy with increasing incidence and poor prognosis (1)(2)(3). The unique anatomical location at the esophagogastric junction (EGJ) complicates early detection, precise diagnosis, and effective treatment strategies (4,5). Although AEG is currently classified within clinical guidelines as a subtype of gastric adenocarcinoma (GAC) and esophageal adenocarcinoma (EAC) for management purposes (6,7), emerging evidence suggests that it possesses distinct molecular characteristics, metastatic behaviors, and responses to therapy, highlighting the necessity for tailored diagnostic and treatment approaches (8,9). Despite advancements in molecular subtyping (4,(10)(11)(12)(13), the mechanisms driving AEG progression, particularly the interplay between tumor heterogeneity, metabolic reprogramming, and the tumor microenvironment (TME), remain inadequately understood. > Recent studies emphasize that metabolic reprogramming not only supports tumor cell proliferation but also actively influences the immunosuppressive TME by modulating immune cell functions (14,15). Tumor cells preferentially utilize glycolysis or glutaminolysis to sustain rapid growth, while accumulating immunosuppressive metabolites which impair cytotoxic T cells activation and promotes the expansion of regulatory T cells and tumor-associated macrophages (TAMs), facilitating immune evasion (16). Therefore, understanding the metabolic alterations in AEG tumor cells and their interactions with the TME is essential for improving patient outcomes, as these processes may explain the limited effectiveness of immune therapies and reveal new therapeutic targets to disrupt tumor progression and enhance treatment efficacy. > Apolipoprotein E (APOE), a secreted protein, traditionally recognized for its role in lipid metabolism and neurodegenerative diseases (17), is increasingly implicated in immune regulation and cancer progression.

[8] EZH2 regulates oncomiR-200c and EMT markers in esophageal squamous cell carcinomas

  • Authors: Fatemeh Nourmohammadi, M. Forghanifard, M. Abbaszadegan, V. Zarrinpour
  • Year: 2022
  • Venue: Scientific Reports
  • URL: https://www.semanticscholar.org/paper/440611350be2b54681a6f1b4d777c783f217c66c
  • DOI: 10.1038/s41598-022-23253-2
  • PMID: 36316365
  • PMCID: 9622866
  • Citations: 16
  • Influential citations: 1
  • Summary: It is demonstrated that EZH2 regulates the expression of miR-200c and critical EMT genes, implying that overexpression of Zeb2, Fibronectin, N-cadherin, and Vimentin lead to a mesenchymal phenotype and morphology while underexpressive of epithelial genes, enhance cell migration after enforced expression of EZh2 in ESCCs.
  • Evidence snippets:
  • Snippet 1 (score: 0.433) > Esophageal cancer (EC) is the seventh most common cancer and the sixth leading cause of cancer-related mortality worldwide with five-year survival rates of less than 20% 1 . EC presents two major histological types including esophageal adenocarcinoma and esophageal squamous cell carcinoma (ESCC) 2 . ESCC is considered as the main histological type (90% of patients) with poor prognosis in the East and the Middle East of Asia, Africa, South America, and Southern Europe [3][4][5] . Although extensive studies have been performed on the ESCC tumorigenesis, the cellular and molecular mechanisms of ESCC progression and development are inadequately identified. Metastasis, tumor relapses and drug resistance are three major difficulties in the treatment of the ESCC malignancy which are associated with high morbidity and mortality of the disease 6 . > Presented treatments for ESCC are including esophagectomy, local mucosal resection or ablation therapies, chemotherapy, and radiation therapy which are approved by the National Comprehensive Cancer Network (NCCN). For many clinical consequences, there are no sufficient conclusive results to assist EC treatment. Esophagectomy, as one of the most complicated cancer surgeries, has a 5% in-hospital mortality rate and a recovery period of nearly a year 7 . Due to the poor prognoses, esophageal cancer almost found at an advanced stage when traditional treatment modalities cannot accomplish the therapy 8 . Furthermore, a large proportion of treated patients (60-70%) do not respond well to neoadjuant therapies and experience serious side effects (vomiting, fluid and electrolyte imbalance, stomatitis/mucositis, renal, hearing, and peripheral neuropathy [8][9][10] . > Vector, kindly provided by Dr. Moein Farshchian, (Molecular Medicine Research Department, ACECR-Khorasan Razavi Branch, Mashhad, Iran) was used to downregulate EZH2 in YM-1 and KYSE-30 cells 37 .

[9] Barrett's esophagus in 2016: From pathophysiology to treatment.

  • Authors: I. Martinucci, N. de Bortoli, S. Russo, L. Bertani, M. Furnari et al.
  • Year: 2016
  • Venue: World journal of gastrointestinal pharmacology and therapeutics
  • URL: https://www.semanticscholar.org/paper/c05b24bddd810b382a8a7ec3f2989bb0ddae929b
  • DOI: 10.4292/wjgpt.v7.i2.190
  • PMID: 27158534
  • Citations: 22
  • Summary: The recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE, and should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs.
  • Evidence snippets:
  • Snippet 1 (score: 0.433) > Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett's esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE.

[10] 1H-NMR based metabonomic profiling of human esophageal cancer tissue

  • Authors: Liang Wang, Jie Chen, Longqi Chen, P. Deng, Q. Bu et al.
  • Year: 2013
  • Venue: Molecular Cancer
  • URL: https://www.semanticscholar.org/paper/e797757fd3d4ff2b3823ff07c621e2333cd4ac7f
  • DOI: 10.1186/1476-4598-12-25
  • Citations: 11
  • Summary: These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer, provide a promising molecular diagnostic approach for clinical diagnosis of human EsophageAL cancer and a new direction for the mechanism study.
  • Evidence snippets:
  • Snippet 1 (score: 0.429) > The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Specially, those that involves in progression of disease would be helpful to mechanism research. In the present study, we investigated the distinguishing metabolites in human esophageal cancer tissues (n = 89) and normal esophageal mucosae (n = 26) using a 1H nuclear magnetic resonance (1H-NMR) based assay, which is a highly sensitive and non-destructive method for biomarker identification in biological systems. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant anlaysis (OPLS-DA) were applied to analyse 1H-NMR profiling data to identify potential biomarkers. The constructed OPLS-DA model achieved an excellent separation of the esophageal cancer tissues and normal mucosae. Excellent separation was obtained between the different stages of esophageal cancer tissues (stage II = 28; stage III = 45 and stage IV = 16) and normal mucosae. A total of 45 metabolites were identified, and 12 of them were closely correlated with the stage of esophageal cancer. The downregulation of glucose, AMP and NAD, upregulation of formate indicated the large energy requirement due to accelerated cell proliferation in esophageal cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal cancer tissue revealed the activation of fatty acids metabolism, which could satisfy the need for cellular membrane formation. Other modified metabolites were involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA and TMA. These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer. Our findings firstly identify the distinguishing metabolites in different stages of esophageal cancer tissues, indicating the attribution of metabolites disturbance to the progression of esophageal cancer. The potential biomarkers provide a promising molecular diagnostic approach for clinical diagnosis of

[11] Single-Cell Analysis Reveals Early Manifestation of Cancerous Phenotype in Pre-Malignant Esophageal Cells

  • Authors: Jiangxin Wang, Xu Shi, Roger H. Johnson, L. Kelbauskas, Weiwen Zhang et al.
  • Year: 2013
  • Venue: PLoS ONE
  • URL: https://www.semanticscholar.org/paper/7ba7fbaeed83cfa22c27647f30449ee513d85b2b
  • DOI: 10.1371/journal.pone.0075365
  • PMID: 24116039
  • PMCID: 3792915
  • Citations: 10
  • Influential citations: 2
  • Summary: This study proposes that mitochondria may be one of the key factors in pre-malignant progression in BE, and shows significant differences between metaplastic and dysplastic BE cells in both average values and single-cell parameter distributions of mtDNA copy numbers, mitochondrial function, and mRNA expression levels of studied genes.
  • Evidence snippets:
  • Snippet 1 (score: 0.429) > Esophageal adenocarcinoma (EAC) is a highly lethal cancer type and is believed to develop from esophageal epithelial cells through a series of complex, step-wise transformations at the biomolecular level [1][2][3][4][5][6]. Once transformed, EAC cells produce significantly higher levels of antioxidant molecules making them resistant to elevated levels of reactive oxygen species (ROS) [2]. Although recent studies have shown that the transformation sequence involves the development of hyperplasia and metaplasia caused by chronic inflammation of the squamous esophageal epithelium, followed by multifocal dysplasia, carcinoma in situ and, finally, invasive EAC [1,7,8], the detailed molecular mechanism underlying this transformation remains to be clarified. > Hypoxia plays a pivotal role in cancer [9][10][11][12][13][14][15][16]. As in almost all solid tumors, oxygen supply to cancer cells is greatly compromised due to the uncontrolled cell growth and inadequate development of the microvasculature. The mitochondrion, the powerhouse of the cell and the major source of adenosine triphosphate (ATP) in normal cells, is the place where oxidative phosphorylation (OXPHOS) takes place. Mitochondria have also been found to play a major role in programmed cell death, or apoptosis, and their dysfunction is associated with a variety of diseases. For example, variations in the mitochondrial DNA (mtDNA) copy number have been associated not only with different cellular physiological conditions but also with diverse changes of internal and external microenvironments [17,18]. It has been demonstrat-ed that mitochondria can generate increased levels of ROS during hypoxia [19], which led to the postulate that mitochondria, the primary target for oxidative damage, can function as an endogenous oxygen sensor. > One of the most important factors determining drug response and aggressiveness of tumors is the large intratumoral heterogeneity.

[12] CRISPR/Cas9 Screening Highlights PFKFB3 Gene as a Major Contributor to 5-Fluorouracil Resistance in Esophageal Cancer

  • Authors: Feng Xue, Hai Yang, Pengyang Xu, Shuman Zhang, N. Britzen-Laurent et al.
  • Year: 2025
  • Venue: Cancers
  • URL: https://www.semanticscholar.org/paper/79b28cf36bb8a53d3cb31ec9abfc975b9a190e19
  • DOI: 10.3390/cancers17101637
  • PMID: 40427135
  • PMCID: 12109790
  • Citations: 1
  • Summary: It is found that the loss of the PFKFB3 gene enhances resistance to 5-FU through different molecular pathways in various cell lines, which may help predict which patients are more likely to develop resistance to 5-FU.
  • Evidence snippets:
  • Snippet 1 (score: 0.423) > Esophageal cancer is the eighth most common cancer and the sixth most common cause of death worldwide [1], with more than 0.6 million new cases of esophageal cancer and 0.54 million deaths worldwide in 2020 [2]. The predominant histological types of esophageal cancer are squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), and ESCC comprises the majority of esophageal cancers globally [2]. The incidence of these two histologic subtypes has significant geographical differences, with EAC being more prevalent in North America, Australia and European countries, and ESCC having a relatively high incidence in East Asia, South America and East Africa [2,3]. > ESCC has a high degree of malignancy. Its treatment regimen is dependent on the tumor stage and the general status of patients. Patients who have locally advanced or disseminated disease at diagnosis should be treated with a systemic regimen [4] and 5-FU is one of the most commonly used chemotherapy drugs [5]. In recent years, immunotherapy has revolutionized the treatment landscape of esophageal cancer, particularly with the advent of immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. The phase III KEYNOTE-590 clinical trial demonstrated that the addition of pembrolizumab to standard chemotherapy (5-FU and cisplatin) significantly improved overall survival and progressionfree survival in patients with advanced esophageal cancer, establishing chemoimmunotherapy as the new first-line treatment standard [6,7]. Despite these advances, intrinsic and acquired resistance to chemotherapy remains a major clinical challenge, often compromising long-term therapeutic efficacy. Therefore, understanding the molecular mechanisms driving chemoresistance is essential for developing more effective and durable treatment strategies. > Over the past decade, as the most advanced gene editing technology, clustered regularly interspaced short palindromic repeats and CRISPR-associated protein9 (CRISPR/Cas9) have been widely used in the field of medical research [8][9][10].

[13] Down-Regulation of MiR-1294 is Related to Dismal Prognosis of Patients with Esophageal Squamous Cell Carcinoma through Elevating C-MYC Expression

  • Authors: Kai Liu, Liyi Li, Aizemaiti Rusidanmu, Yongqing Wang, X. Lv
  • Year: 2015
  • Venue: Cellular Physiology and Biochemistry
  • URL: https://www.semanticscholar.org/paper/f978967e1fbb497423a7b2338075c1f4f8060b01
  • DOI: 10.1159/000374056
  • PMID: 25925090
  • Citations: 39
  • Influential citations: 1
  • Summary: Investigation in patients with esophageal squamous cell carcinoma and its effect on prognosis found down-regulation of miR-1294 correlates with poor prognosis of ESCC, partially due to the reduced function of c-MYC.
  • Evidence snippets:
  • Snippet 1 (score: 0.423) > Esophageal cancer is now the eighth most common cancer and the sixth most common cause of cancer deaths worldwide. Histologically, in approximately 95% of cases, the disease occurs as esophageal squamous cell carcinoma (ESCC) or esophageal adenocarcinoma (EAC). Barrett's adenocarcinoma is the most rapidly increasing cancer in Western countries, while esophageal squamous cell carcinoma (ESCC) dominant in East Asia. Although surgical and medical treatments for ESCC has been improved in recent years, the overall outcome of patients with ESCC is dismal, with a 5 year survival rate of less than 10%. And the diagnosis of early stage ESCC is also challenging [1]. Thus, elucidating the molecular mechanisms of ESCC pathogenesis will help to identify specific tumor markers for early detection, risk assessment, and therapeutic target. > MicroRNA (miRNA) is a kind of short non-coding RNAs that suppress the expression of protein coding genes by partial complementary binding, especially to the 3' untranslated regions (UTRs) of messenger RNAs (mRNAs). MiRNA expression alterations are involved in the initiation, progression, and metastasis of human cancer and it is believed that miRNAs function both as tumor suppressors and oncogenes in cancer development [2,3]. > C-Myc is a transcription factor acting as a master regulator of genes involved in cell cycle progression, cell growth, differentiation, metabolism and apoptosis. It is also a potent cellular oncogene that is found frequently deregulated in human cancers. This pathological upregulation is frequently due to chromosomal translocations leading to promoter rearrangement [4][5][6][7], gene amplification [7] and viral mediated insertional mutagenesis [8]. There is also evidence that c-MYC expression is suppressed by miRNAs [9,10]. > In this study, we first detected 6 candidate miRNAs expression in 79 ESCC tissues and found the expression of miR-205, miR-34b and miR-1294 was significantly reduced.

[14] Surgical Timing and Outcomes in Esophageal Cancer: Insights from One- and Two-Stage Esophagectomies in a Polish Cohort

  • Authors: B. Strzelec, P. Chmielewski, Wojciech Kielan, Julia Rudno-Rudzińska
  • Year: 2025
  • Venue: Journal of Clinical Medicine
  • URL: https://www.semanticscholar.org/paper/1b7ab51c8d096577639a3f9ed7a0ced7fb126782
  • DOI: 10.3390/jcm14124301
  • PMID: 40566043
  • PMCID: 12194437
  • Citations: 1
  • Summary: Postoperative complications remain a significant challenge in esophageal cancer surgery, particularly in the context of advanced disease or neoadjuvant chemoradiotherapy, and underscore the necessity for precise surgical planning and comprehensive postoperative care to mitigate risks and optimize patient outcomes.
  • Evidence snippets:
  • Snippet 1 (score: 0.411) > Esophageal cancer (EC) is a highly lethal malignancy that represents a major global health burden, with approximately 500,000-600,000 new cases and 500,000 deaths annually despite its relatively low incidence [1][2][3][4][5]. Patients typically present with dysphagia, weight loss, and cachexia, reflecting the disease's rapid progression and poor prognosis [3]. Despite advances in multimodal therapy, including immunotherapy and targeted approaches, five-year survival remains below 20% in most cohorts [4][5][6]. Diagnosis typically involves high-resolution endoscopic ultrasonography and computed tomography (CT), with histopathological staging guiding treatment decisions. The advanced age at presentation, combined with EC's aggressive biology, places considerable strain on health systems and underscores the urgent need for novel therapies targeting its molecular drivers and strategies to improve early detection. > Two predominant subtypes of EC are squamous cell carcinoma (SCC) and adenocarcinoma (AC), which differ markedly in epidemiology, pathophysiology, and clinical presentation. SCC is strongly associated with heavy tobacco and alcohol use, whereas AC is more commonly linked to obesity and chronic gastroesophageal reflux disease (GERD) [3,7]. SCC accounts for approximately 90% of cases worldwide, with a higher prevalence in regions such as Asia, East Africa, and South America [8], while AC predominates in Western countries [9]. Both subtypes have identifiable precursor lesions that, if detected early, are amenable to endoscopic ablative therapies. Nonetheless, the majority of cases present at locally advanced or metastatic stages, requiring complex, multimodal treatment approaches. Effective management of EC typically combines chemotherapy, chemoradiotherapy (CRT), and surgical resection, tailored to the patient's disease stage and functional status. For advanced or metastatic cases, palliative chemotherapy remains the cornerstone of care, with targeted agents, such as trastuzumab for HER2-positive tumors, offering survival benefits [1].

[15] miR-25 promotes metastasis via targeting FBXW7 in esophageal squamous cell carcinoma.

  • Authors: Y. Hua, Kai Zhao, G. Tao, C. Dai, Yuting Su
  • Year: 2017
  • Venue: Oncology reports
  • URL: https://www.semanticscholar.org/paper/373d9481658b0668ca23d810fbca4acc48c8382c
  • DOI: 10.3892/or.2017.5995
  • PMID: 29048664
  • Citations: 16
  • Summary: The present study supports the potential of miR-25 as a prognostic predictor with its high expression in cancer tissues and its association with tumor progression by targeting FBXW7 in ESCC.
  • Evidence snippets:
  • Snippet 1 (score: 0.411) > Esophageal cancer is a highly lethal malignancy. As the main type of esophageal cancer, esophageal squamous cell carcinoma (ESCC) accounts for ~90% of all esophageal cancer cases (1,2). However, patients with ESCC are usually diagnosed at advanced stages (3). Recently, advances in the application of combined chemotherapy and radiotherapy, alone or as an adjunct regimen to surgery, have improved the prognosis of ESCC patients (4). Cumulative evidence suggests that a number of oncogenic and tumor-suppressive genes are associated with the initiation and progression of ESCC (3). Yet, the molecular mechanisms underlying the deregulation of the cellular phenotype in ESCC have not been fully clarified. Elucidation of the genetic alterations and underlying molecular pathways involved in ESCC may facilitate the identification of novel targets, as well as improve disease diagnosis and therapy. > MicroRNAs (miRNAs), a kind of endogenous RNA gene products consisting of 18-25 nucleotides, have been identified as important regulators of human malignancies (5). Recently, using detection techniques such as RNA sequencing and microarray, there are various findings that have illustrated the expression profile of miRNAs in ESCC. Moreover, research concerning miRNAs and their target genes and the molecular mechanisms involved in the carcinogenesis of ESCC suggests the enormous therapeutic-clinical potential of miRNAs (6). miR-25 is one of the oncogenes has been reported to be upregulated in several cancers such as hepatocellular carcinoma (7), lung (8), prostate (9) and gastric cancer (10). In addition, plasma miRNA profiles have revealed miR-25 as a novel diagnostic and monitoring biomarker in ESCC (11). Desmocollin 2 (DSC2), a desmosomal cadherin protein which promotes cell aggressiveness by redistributing adherens junctions and activating β-catenin signaling in ESCC, has been identified as a downstream target of miR-25 (12).

[16] LAMP2 as a Biomarker Related to Prognosis and Immune Infiltration in Esophageal Cancer and Other Cancers: A Comprehensive Pan-Cancer Analysis

  • Authors: Shangyi Liu, Xiao-min Li, Dan Liu, Shugang Xie, Shao-bo Zhang et al.
  • Year: 2022
  • Venue: Frontiers in Oncology
  • URL: https://www.semanticscholar.org/paper/748f52adcc443c266409d942de0d36882b77e7f8
  • DOI: 10.3389/fonc.2022.884448
  • PMID: 35530327
  • PMCID: 9069144
  • Citations: 12
  • Summary: This study obtained RNA-sequencing raw count data and corresponding clinical information for ESCA samples from The Cancer Genome Atlas and Gene Expression Omnibus databases and performed the pan-cancer analysis of LAMP2, indicating that LAMP 2 expression was significantly upregulated in ESCA and various human cancers.
  • Evidence snippets:
  • Snippet 1 (score: 0.411) > Esophageal cancer (ESCA), which includes esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is a leading cause of cancer-related mortality worldwide (1). Currently, the diagnosis and prognosis of ESCA depend on various factors, including the clinicopathological stage, histological type, tumor size, age, and treatment sensitivity. Early clinical symptoms in patients with ESCA are usually insidious and mild (2,3). Most patients have a locally advanced or metastatic disease at the time of diagnosis. Despite recent advances in the treatment of ESCA, including molecularmarker-based diagnosis, radiomics, targeted therapies, and immunotherapy, long-term survival rates remain relatively low (4)(5)(6). Therefore, it will be of great clinical value to understand the molecular mechanisms underlying the occurrence and progression of ESCA in order to explore effective and novel biomarkers and improve the diagnosis and prognosis of patients with ESCA. > The metabolic function of lysosomes is extremely important and increasingly recognized. The role of lysosomes was not novel in the degradation of cellular machinery (3). Previous research has shown that the functional status and spatial distribution of lysosomes are associated with the proliferation, energy metabolism, invasion and metastasis, immune escape, drug resistance, and tumor-associated angiogenesis of cancer cells (7)(8)(9). The LAMP2 gene encodes lysosomal-associated membrane protein 2 (LAMP2), which is a single transmembrane protein located at the limiting membrane of lysosomes and late nuclear endosomes. LAMP2 has three isoforms, LAMP2a, 2b, and 2c, which are involved in autophagy (10). Accumulating evidence indicates that lysosomes play an important part in various cancers; this has raised interest in the role of LAMP2 in cancer progression.

[17] Novel BRCA2-Interacting Protein, LIMD1, Is Essential for the Centrosome Localization of BRCA2 in Esophageal Cancer Cell

  • Authors: Xiaobin Hou, Tinghui Li, Z. Ren, Yang Liu
  • Year: 2016
  • Venue: Oncology Research
  • URL: https://www.semanticscholar.org/paper/a9f1def011bdc56981129de70ea810bf526ea0d0
  • DOI: 10.3727/096504016X14652175055765
  • PMID: 27656835
  • PMCID: 7838625
  • Citations: 10
  • Summary: LIMD1 is a novel BRCA2-interacting protein and is involved in the centrosome localization of BRC a2 and suppression of LIMD1, causing abnormal cell division in EC cells.
  • Evidence snippets:
  • Snippet 1 (score: 0.410) > Esophageal cancer (EC) is a cancer arising from the esophagus. It is the eighth most common cancer worldwide, with 400,000 deaths every year (1). The major histological types include esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) (2). The risk factors for both types of EC have been proven to be different (3). The most common causes of ESCC are smoking, alcohol, hot drinks, and poor diet, while the most common causes of EAC are smoking, obesity, and acid reflux (4). Of note, the genetic aspect is a risk factor in both types of EC. The treatment of EC is based on the cancer's type, stage, and location. Surgery is generally accepted as the main treatment, and chemotherapy or radiation therapy is used along with surgery (5). Despite the amount of effort that has gone into developing treatments for this disease, outcomes remain unfavorable, and the overall 5-year survival rates are around 16.9% to 20.9% (6). > Breast cancer 2, early onset (BRCA2), together with breast cancer 1, early onset (BRCA1), are major hereditary breast cancer susceptibility genes (7). Multiple studies have demonstrated that alteration of the BRCA2 gene gives an increased risk factor for tumorigenesis and progression in a variety of cancers, including breast cancer, ovarian cancer, and EC (8,9). The germline mutation of the BRCA2 gene has been monitored in several high-risk EC populations from northwest China, northeast India, and Turkmen of Iran. The BRCA2 mutation has been identified as a vital risk factor in EC (10). Clinical investigations in patients with EC have shown that BRCA2 might impact patient survival and could be a potential genomic predictor of clinical response to DNA-damaging treatment (11). However, the detailed function of BRCA2 on EC cells and its underlying molecular mechanisms have not been well clarified. > The centrosome is an important organelle in cells and is closely associated to mitosis.

[18] Association between ALDH2 Glu487Lys polymorphism and the risk of esophageal cancer

  • Authors: Kang Liu, Guiqin Song, Xiaoyan Zhu, Xiaolin Yang, Yuewu Shen et al.
  • Year: 2017
  • Venue: Medicine
  • URL: https://www.semanticscholar.org/paper/6d97adb134dd29036d607c288e9b377f67931824
  • DOI: 10.1097/MD.0000000000006111
  • PMID: 28422823
  • PMCID: 5406039
  • Citations: 11
  • Summary: There was a strong association between ALDH2 Glu487Lys polymorphism and the risk of esophageal cancer and a negative association was observed under homozygote comparison.
  • Evidence snippets:
  • Snippet 1 (score: 0.410) > Esophageal carcinoma (EC) is the 8th most common cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) are 2 major histological types. [1] It has been reported that the highest incidences occurred in Asian countries, such as China, Iran, and Japan. [2] Despite of the use of surgery in combination with radiotherapy and chemotherapy, the overall 5-year survival rate remains <40% in patients with advanced disease. [3] erefore, risk evaluation and elucidation of molecular mechanisms are required to improve treatment efficacy for patients with EC. > EC is a complex disease, and it is well accepted that environment factors play an important role as genetic factors in the development of EC. Alcohol consumption has been considered as a high-risk factor for EC patients. [4] Alcohol itself is not a carcinogen, but its metabolite acetaldehyde has carcinogenic property. Alcohol in humans can be oxidized to acetaldehyde, which is further oxidized into harmless acetate by aldehyde dehydrogenases (ALDHs). ALDH2 is one of the major enzymes to eliminate acetaldehyde, and thus determines blood acetaldehyde concentrations after drinking. ALDH2 displays a polymorphism that may affect alcohol-oxidizing capacity. A single point mutation of a lysine amino acid has been found at residue 487 instead of glutamic acid in ALDH2 gene (ALDH2 Glu487Lys), resulting in a reduced enzyme activity. Individuals with the ALDH2 Lys allele have a high concentration of blood acetaldehyde after drinking alcohol, thus enhances the risk for esophageal cancer. [5] The polymorphisms of ALDH2 associated with the risk of esophageal cancer have been described in several studies, but the results are still inconsistent. > Meta-analysis provides an opportunity to aggregate information from multiple studies, improving statistical power by increasing the sample size to precisely evaluate genetic polymorphisms effects on disease susceptibility.

[19] Downregulation of Ubiquitin Inhibits the Aggressive Phenotypes of Esophageal Squamous Cell Carcinoma

  • Authors: Yi Gao, W. Mo, Li Zhong, Huimin Jia, Yiren Xu et al.
  • Year: 2020
  • Venue: Technology in Cancer Research & Treatment
  • URL: https://www.semanticscholar.org/paper/e33d9ff58b30ff806b5bf28ae87ef61caf23aaa3
  • DOI: 10.1177/1533033820973282
  • PMID: 33176591
  • PMCID: 7672754
  • Citations: 5
  • Summary: Downregulation of ubiquitin suppresses the aggressive phenotypes of esophageal squamous cell carcinoma cells by complex mechanisms; Ubiquitin may represent a novel target for the treatment of esphageal Squamous Cell carcinoma.
  • Evidence snippets:
  • Snippet 1 (score: 0.408) > Esophageal cancer is the seventh most common cancer and the sixth most common cause of cancer-related mortality. In 2018, 572,034 new cases of esophageal cancer and 508,585 esophageal cancer-related deaths were reported; more than half of these deaths occurred in China. 1 There are two main histological types of esophageal cancer: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. In China, approximately 95% of esophageal cancer cases are of the ESCC type. Despite continuous advances in the management of cancer, esophageal cancer still has an unfavorable prognosis because of its late diagnosis and rapid metastasis. 2][3] However, with the large population base of China, the national cancer burden continues to rise, and the underlying molecular mechanisms of ESCC remain unclear. > The stability and correct degradation of intracellular proteins is essential for maintaining normal cell functions. It is well accepted that cellular proteins are degraded by three main proteolytic pathways: the ubiquitin-proteasome proteolytic pathway, lysosome-mediated proteolysis, and the caspase hydrolysis pathway. 4 6][7] Lack of proper control over the UPS may contribute to pathological conditions, including cancer. 8 Proteasome inhibitors, such as bortezomib and carfilzomib, have emerged as novel and promising anticancer drugs in clinical applications. 9,10 Ubiquitin is a small 76-amino acid protein (8.6 kDa) that is highly conserved among eukaryotes. 11 Ubiquitin is encoded by four different genes: ubiquitin B (UBB), ubiquitin C (UBC), UBA52, and RPS27A. The UBA52 and RPS27A genes encode the fusion ribosomal proteins L40 and S27a, respectively, and are thought to be essential for protein synthesis. The polyubiquitin precursor proteins are encoded by the UBB and UBC genes. 12

[20] Differential Expression of Desmocollin2, Desmoglein2, and Plakophilin2 in the Progression of Esophagitis to Esophageal Adenocarcinoma

  • Authors: Yun-fei Wu, Nannan Liu, Wanlan Bo, L. Zhuang
  • Year: 2021
  • Venue: Unknown venue
  • URL: https://www.semanticscholar.org/paper/1c0b85bf0f7c4c8e6969530a205c9f3f71a14bd8
  • DOI: 10.21203/rs.3.rs-154489/v1
  • Summary: DSC2, DSG2, and PKP2 may play an important role in the progression of esophagitis to EAC and their expression levels may therefore be utilized as molecular biomarkers for early diagnosis and targeted therapy for EAC.
  • Evidence snippets:
  • Snippet 1 (score: 0.406) > Esophageal cancer is the eighth most common cancer worldwide and is associated with high morbidity and mortality. Since the 1970s [4] , the incidence of esophageal adenocarcinoma (EAC) has increased in many Western and several Asian countries [1][2][3] by approximately 600%, with the incidence of adenocarcinoma type exceeding those of esophageal squamous cell carcinoma (ESCC) [5] . China has approximately 18% of all cases worldwide given its large population [5] . The overall mortality of EAC is high, with a 5-year survival rate of less than 15% [4] , primarily because of patients presenting and diagnosed at an incurable late-stage [6,7] . > Although several risk factors have been associated with EAC, Gastroesophageal re ux disease (GERD) represents the strongest risk factor [8] that has been demonstrated in several population-based studies [6,9] . GERD causes re ux esophagitis, leading to Barrett's esophagus and the dysplasia of the esophagus, which predisposes to esophageal adenocarcinoma [10,11] . The molecular mechanisms underlying such progression of a chronic benign condition to esophageal carcinogenesis remain to be elucidated. > Previously, we presented a functional module-based approach to explore link between in ammation and esophagus cancer based on GEO database [12] . We observed a functional module containing genes Desmocollin2(DSC2), Desmoglein2(DSG2), and Plakophilin2(PKP2), was served as both in ammation and cancer module. DSG2, PKP2 and DSC2 supposed to play a vital role in progression from esophagitis to esophageal cancer. However, the mechanism underlying the effect of the three genes on tumor progression remains unknown, with only a limited number of studies reporting on the role of them in esophageal cancer.

Notes

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