🏷

Classifications

ICD-O Morphology

Harrison's Part

🔗

Mappings

MONDO

MONDO:0005075 thyroid gland papillary carcinoma

MONDO provides an exact disease term for papillary thyroid carcinoma; this is the same term used as `disease_term` for this entry.

NCIT

NCIT:C4035 Thyroid Gland Papillary Carcinoma

NCIT provides an exact neoplasm term for papillary thyroid carcinoma; cross-referenced from MONDO:0005075.

NCIT

NCIT:C4035 Thyroid Gland Papillary Carcinoma

NCIT provides an exact neoplasm term for papillary thyroid carcinoma; cross-referenced from MONDO:0005075.

◆

Subtypes

3

Classical Papillary Thyroid Carcinoma

Conventional papillary thyroid carcinoma with papillary architecture and the characteristic nuclear features used for diagnosis.

Follicular Variant Papillary Thyroid Carcinoma

Papillary thyroid carcinoma with predominantly follicular architecture and papillary-type nuclear features. Often aligns with a more RAS-like molecular profile than classical PTC.

Tall Cell Variant Papillary Thyroid Carcinoma

Aggressive histologic variant enriched for BRAF V600E, extrathyroidal extension, and recurrence risk.

⚙

Pathophysiology

3

Driver Alterations in Thyroid Follicular Cells

Early oncogenic alterations in papillary thyroid carcinoma commonly include BRAF V600E, RET/PTC rearrangements, and RAS-family mutations. These driver events arise in thyroid follicular cells and establish the genotype-phenotype patterns that distinguish conventional papillary tumors from more follicular-patterned neoplasms.

thyroid follicular cell CL:0002258

thyroid gland UBERON:0002046

Downstream

MAPK Pathway Hyperactivation Driver mutations and fusions converge on persistent mitogenic signaling

Show evidence (2 references)

PMID:39502057 SUPPORT Human Clinical

"The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations."

Supports the major early driver classes emphasized in papillary thyroid carcinoma.

PMID:41175860 SUPPORT Human Clinical

"In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations."

Anchors the characterization of these driver events as the primary (early) molecular alterations in follicular-cell-derived thyroid tumors.

MAPK Pathway Hyperactivation

Driver alterations converge on chronic MAPK signaling, which promotes thyroid follicular cell proliferation and malignant transformation. BRAF-like tumors especially depend on this pathway and often show loss of thyroid differentiation programs relevant to iodine handling.

MAPK cascade GO:0000165 ↑ INCREASED

Downstream

Aggressive Progression and Reduced Differentiation Additional oncogenic hits superimposed on driver signaling promote dedifferentiation and treatment resistance

Show evidence (2 references)

PMID:41175860 SUPPORT Human Clinical

"In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations."

Supports the dominant BRAF-like and RAS-like molecular programs that organize papillary thyroid carcinoma biology.

PMID:41368991 SUPPORT Human Clinical

"BRAF V600E, the most common oncogenic driver in papillary thyroid carcinoma, activates the MAPK pathway and suppresses genes involved in iodine metabolism and differentiation."

Supports the role of BRAF-driven MAPK activation and reduced differentiation in a major papillary thyroid carcinoma subset.

Aggressive Progression and Reduced Differentiation

A subset of papillary thyroid carcinomas acquires additional alterations such as TERT promoter mutation, TP53 disruption, and aberrant PI3K-PTEN-AKT signaling. These changes are associated with progression toward more aggressive, less-differentiated, and radioiodine-refractory disease.

phosphatidylinositol 3-kinase/protein kinase B signal transduction GO:0043491 ↑ INCREASED cell differentiation GO:0030154 ↓ DECREASED

Show evidence (1 reference)

PMID:41175860 SUPPORT Human Clinical

"Progression of thyroid tumors to advanced and less-differentiated carcinomas requires additional oncogenic alterations, including TP53 and TERT promoter mutation, and aberrant PI3K-PTEN-AKT signaling."

Supports the progression model linking additional alterations to aggressive and less-differentiated thyroid carcinoma states.

✶

Histopathology

3

Papillary Thyroid Carcinoma VERY_FREQUENT

Papillary thyroid carcinoma is the dominant malignant thyroid histology and includes classical, follicular variant, tall cell, and other less common morphologic forms.

Show evidence (1 reference)

PMID:21221869 SUPPORT Human Clinical

"Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies."

Supports papillary thyroid carcinoma as the predominant malignant thyroid histology.

Papillary-Type Nuclear Features VERY_FREQUENT

The hallmark diagnostic nuclear features of papillary thyroid carcinoma include nuclear enlargement with optically clear (ground-glass) chromatin ("Orphan-Annie eye" nuclei), longitudinal nuclear grooves, and intranuclear cytoplasmic pseudoinclusions. These papillary-type nuclear changes are required criteria for histological and cytological diagnosis, distinguishing PTC from benign follicular lesions. Their frequency correlates with BRAF V600E mutation in classical and tall-cell subtypes.

Show evidence (1 reference)

PMID:26271724 SUPPORT Human Clinical

"nuclear grooves, optically clear nuclei, tall cells within the tumor"

Multicenter pathological analysis of papillary thyroid microcarcinomas identifies nuclear grooves and optically clear nuclei as characteristic microscopic features correlated with BRAF V600E.

Psammoma Bodies

Psammoma bodies are concentrically laminated calcified structures that form by dystrophic calcification of infarcted papillae or necrotic neoplastic cells. They are a diagnostically useful but non-universal finding in papillary thyroid carcinoma. Although their sensitivity is low (they are absent in a substantial minority of PTCs), their presence is highly specific for malignancy and for PTC in particular, especially when encountered in cervical lymph node tissue. Identification of psammoma bodies alone in a cervical lymph node is considered evidence of metastatic PTC even when viable tumor cells are absent.

Show evidence (1 reference)

PMID:37181946 SUPPORT Human Clinical

"Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%."

Retrospective study of 337 PTC patients confirms psammoma bodies as perfectly specific for PTC on FNA cytology despite lower sensitivity, supporting their role as a high-value diagnostically specific feature.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

2

Cardiovascular 1

Cervical Lymphadenopathy HP:0002716

Show evidence (1 reference)

PMID:29329789 SUPPORT Human Clinical

"Lymph node metastasis (LNM) is frequent in papillary thyroid carcinoma (PTC) and is associated with a poor prognosis."

Systematic review and meta-analysis supports regional lymph node metastasis as a frequent feature of papillary thyroid carcinoma.

Other 1

Thyroid Nodule HP:0025388

Show evidence (1 reference)

PMID:24276450 SUPPORT Human Clinical

"The most common type of cancer was papillary thyroid cancer (84%)."

In a meta-analysis of 18,288 thyroid nodules, papillary thyroid carcinoma was the predominant malignancy identified, consistent with the thyroid nodule being the characteristic presentation of papillary thyroid carcinoma.

🧬

Genetic Associations

4

BRAF (Somatic Activating Mutations)

Gene: BRAF hgnc:1097

Show evidence (3 references)

PMID:41368991 SUPPORT Human Clinical

"BRAF V600E, the most common oncogenic driver in papillary thyroid carcinoma, activates the MAPK pathway and suppresses genes involved in iodine metabolism and differentiation."

Supports BRAF V600E as the dominant papillary thyroid carcinoma driver and a mechanism for MAPK activation.

PMID:41419184 SUPPORT Human Clinical

"Overall, these findings confirm that BRAF V600E mutation is associated with an increased risk of nodal metastasis and recurrence in papillary thyroid carcinoma."

Supports the clinical association between BRAF V600E and adverse recurrence-related features.

PMID:41419184 SUPPORT Human Clinical

"However, its lack of impact on distant metastases and disease-specific mortality limits its role as an independent prognostic marker in clinical decision-making."

The same meta-analysis found no significant association with distant metastases or disease-specific mortality, qualifying BRAF V600E as an incomplete independent prognostic marker.

RET (Somatic Gene Fusions)

Gene: RET hgnc:9967

Show evidence (1 reference)

PMID:39502057 SUPPORT Human Clinical

"The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations."

Supports RET/PTC rearrangements as one of the major recurrent driver classes in papillary thyroid carcinoma.

RAS family genes (Somatic Activating Mutations)

Show evidence (2 references)

PMID:39502057 SUPPORT Human Clinical

"The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations."

Supports RAS-family alterations as recurrent papillary thyroid carcinoma drivers.

PMID:41175860 SUPPORT Human Clinical

"In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations."

Supports the distinction between RAS-like follicular-patterned tumors and BRAF-like conventional papillary carcinomas.

TERT (Somatic Promoter Mutations)

Gene: TERT hgnc:11730

Show evidence (1 reference)

PMID:41175860 SUPPORT Human Clinical

"Progression of thyroid tumors to advanced and less-differentiated carcinomas requires additional oncogenic alterations, including TP53 and TERT promoter mutation, and aberrant PI3K-PTEN-AKT signaling."

Supports TERT promoter mutation as a late progression event in aggressive thyroid carcinoma biology.

💊

Medical Actions

5

Thyroidectomy

Action: Thyroidectomy NCIT:C51648

Surgical resection is the mainstay of treatment for localized papillary thyroid carcinoma.

Radioiodine Therapy

Action: Radioactive Iodine Therapy NCIT:C157968

Radioactive iodine is used selectively after surgery for intermediate-risk, high-risk, or metastatic differentiated thyroid cancer.

Mutation-Directed Targeted Therapy

Action: targeted therapy Ontology label: Targeted Therapy NCIT:C93352

Advanced papillary thyroid carcinoma with actionable driver alterations may be treated with genotype-matched targeted therapy, including RET inhibitors for RET fusion-positive disease and BRAF-directed regimens in BRAF V600E- driven refractory tumors.

Lenvatinib or Sorafenib

Action: targeted therapy Ontology label: Targeted Therapy NCIT:C93352

Agent: lenvatinib CHEBI:85994 sorafenib CHEBI:50924

Multi-kinase inhibitors are standard systemic options for progressive radioiodine-refractory differentiated thyroid cancer when surgery and radioiodine are no longer sufficient.

Cabozantinib

Action: targeted therapy Ontology label: Targeted Therapy NCIT:C93352

Agent: cabozantinib CHEBI:72317

Cabozantinib is a multi-kinase inhibitor (VEGFR2, MET, AXL, RET) used in the second-line setting for radioiodine-refractory differentiated thyroid cancer that has progressed during or after lenvatinib or sorafenib. This VEGFR-TKI-refractory population previously had no standard of care; the randomised placebo-controlled COSMIC-311 trial met its progression-free survival endpoint at interim analysis, at the cost of substantially more grade 3-4 toxicity (palmar-plantar erythrodysaesthesia, hypertension, fatigue).

Show evidence (4 references)

PMID:34237250 SUPPORT Human Clinical

"Patients must have received previous lenvatinib or sorafenib and progressed during or after treatment with up to two VEGFR tyrosine kinase inhibitors."

Defines the second-line, VEGFR-TKI-refractory population in which cabozantinib was evaluated, downstream of the lenvatinib/sorafenib option already curated here.

PMID:34237250 SUPPORT Human Clinical

"cabozantinib showed significant improvement in progression-free survival over placebo: median not reached ... versus 1·9 months (1·8-3·6); hazard ratio 0·22 (96% CI 0·13-0·36; p<0·0001)"

Reports the randomised progression-free survival benefit that supports cabozantinib as an active option after VEGFR-TKI failure.

PMID:34237250 SUPPORT Human Clinical

"Grade 3 or 4 adverse events occurred in 71 (57%) of 125 patients receiving cabozantinib and 16 (26%) of 62 receiving placebo"

Quantifies the grade 3-4 toxicity burden stated in the description, so the efficacy claim is not curated without its safety cost.

+ 1 more reference

🌍

Environmental Factors

1

Ionizing Radiation Exposure

Ionizing radiation is the strongest established environmental risk factor for papillary thyroid carcinoma, especially after childhood or adolescent exposure.

Show evidence (1 reference)

PMID:21221869 SUPPORT Human Clinical

"The most common etiologic factor is radiation"

Supports radiation exposure as the leading established environmental risk factor for papillary thyroid carcinoma.

Mechanism Target:

TRIGGERS Driver Alterations in Thyroid Follicular Cells — Radiation reaching the thyroid causes double-strand breaks whose mis-joining produces the rearrangement-type drivers characteristic of radiation-associated disease, so the exposure reaches this node through a known repair-error step.

Show evidence (1 reference)

PMID:21221869 SUPPORT Human Clinical

"The most common etiologic factor is radiation"

Identifies radiation as the most common etiologic factor for this cancer, the exposure that generates its driver alterations.

🔬

Biochemical Markers

2

Thyroglobulin

Show evidence (2 references)

PMID:21221869 SUPPORT Human Clinical

"Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites."

Supports the diagnostic utility of thyroglobulin immunostaining in papillary thyroid carcinoma at metastatic sites.

PMID:26462967 SUPPORT Human Clinical

"surveillance for recurrent disease using imaging and serum thyroglobulin"

ATA guidelines confirm serum thyroglobulin as a standard postoperative surveillance marker for differentiated thyroid cancer including PTC.

Molecular Driver Testing

Show evidence (1 reference)

PMID:39502057 SUPPORT Human Clinical

"The prognosis of papillary thyroid carcinoma (PTC) is highly dependent on gene mutations and pathologic features."

Supports routine clinical relevance of molecular and pathologic stratification in papillary thyroid carcinoma.

📊

Prevalence

1

Worldwide

Annual Incidence Common

Papillary thyroid carcinoma is the most common thyroid malignancy, constituting more than 70% of all thyroid cancers. Global incidence has been rising substantially over recent decades, driven in part by increased use of thyroid ultrasound and detection of small, clinically occult tumors. Incidence varies markedly by region, with higher rates in countries with widespread thyroid imaging programs (e.g., the United States, South Korea) and lower rates in lower-resource settings. Note: this entry shares MONDO:0005075 with the BRAF_Mutant_Thyroid_Cancer and RET_Fusion_Thyroid_Cancer molecular-subtype sibling entries; these subtypes collectively represent a large proportion of the overall PTC incidence.

Show evidence (2 references)

PMID:21221869 SUPPORT Human Clinical

"Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies."

Establishes PTC as the dominant thyroid cancer histotype comprising over 70% of all thyroid malignancies.

PMID:26462967 SUPPORT Human Clinical

"differentiated thyroid cancer is becoming increasingly prevalent"

ATA 2015 guidelines acknowledge the rising incidence of differentiated thyroid cancer (predominantly PTC).

📊

Related Datasets

3

Whole exome sequencing of papillary thyroid carcinoma in the Chinese population ega:EGAS00001001268

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here we submitted the sequencing results for PTC using 91 tumor-normal pairs through exome sequencing in the Chinese Han population.

human

European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Papillary Thyroid Carcinoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.

The genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis ega:EGAS00001004101

Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland with arelatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, itsignificantly decreases the survival of PTC patients. However, the molecular mechanisms of DMin PTCs have not been systematically studied. We performed whole exome sequencing andGeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched whiteblood cell samples from 20 PTCs with DM and 46 PTCs without DM. We identified somaticmutations, gene fusions and copy number alterations and analyzed their relationships with DM ofPTCs.

human

European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Papillary Thyroid Carcinoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.

Pediatric Papillary Thyroid Carcinoma RNA-Seq ega:EGAS00001005182

Papillary thyroid carcinoma (PTC) is the most common malignancy amongst adolescent and young adult women. Clinical and genomic features of PTC in children differ from those in adults. Historically, a substantial proportion (~50%) of pediatric PTC (PPTC) lack any of the common driver mutations typical of adult PTC. Thus, molecular diagnostics developed for adults may not be valid in children. We applied novel bioinformatic pipelines to RNASeq analysis of pediatric thyroid tumors to identify known and novel fusion oncogenes as drivers of tumorigenesis and to define gene expression patterns among tumors.

human

European Genome-phenome Archive study, matched because the disease is named in the study's own title ("Papillary Thyroid Carcinoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.

🔬

Clinical Trials

1

NCT03690388 PHASE_III ACTIVE_NOT_RECRUITING

COSMIC-311: randomised, double-blind, placebo-controlled phase 3 trial of cabozantinib in radioiodine-refractory differentiated thyroid cancer (papillary or follicular and their variants) progressing after prior VEGFR-targeted therapy. Primary endpoints were objective response rate and progression-free survival.

Show evidence (1 reference)

clinicaltrials:NCT03690388 SUPPORT Human Clinical

"evaluate the effect of cabozantinib compared with placebo on progression free survival (PFS) and objective response rate (ORR) in subjects with Radioiodine-Refractory Differentiated Thyroid Cancer (DTC) who have progressed after prior vascular endothelial growth factor receptor (VEGFR)-Targeted therapy"

The registered trial objective matches the second-line indication curated in the Cabozantinib treatment entry.

{ }

Source YAML

click to show

name: Papillary Thyroid Carcinoma
creation_date: '2026-04-12T05:10:03Z'
description: >-
  Papillary thyroid carcinoma is the most common differentiated thyroid cancer
  arising from thyroid follicular cells. It comprises the majority of thyroid
  malignancies and includes classical, follicular-patterned, and more aggressive
  variants such as tall cell carcinoma. Papillary thyroid carcinoma is typically
  driven by MAPK-pathway activating alterations including BRAF V600E, RET/PTC
  rearrangements, and RAS-family mutations, while additional events such as TERT
  promoter mutation and aberrant PI3K-PTEN-AKT signaling are associated with
  aggressive progression and radioactive iodine-refractory disease. Most cases
  have excellent disease-specific survival, but regional nodal metastasis and
  recurrence remain clinically important.
categories:
- Endocrine Cancer
- Differentiated Thyroid Cancer
parents:
- thyroid carcinoma
has_subtypes:
- name: Classical Papillary Thyroid Carcinoma
  description: >-
    Conventional papillary thyroid carcinoma with papillary architecture and the
    characteristic nuclear features used for diagnosis.
- name: Follicular Variant Papillary Thyroid Carcinoma
  description: >-
    Papillary thyroid carcinoma with predominantly follicular architecture and
    papillary-type nuclear features. Often aligns with a more RAS-like molecular
    profile than classical PTC.
- name: Tall Cell Variant Papillary Thyroid Carcinoma
  description: >-
    Aggressive histologic variant enriched for BRAF V600E, extrathyroidal
    extension, and recurrence risk.
pathophysiology:
- name: Driver Alterations in Thyroid Follicular Cells
  description: >-
    Early oncogenic alterations in papillary thyroid carcinoma commonly include
    BRAF V600E, RET/PTC rearrangements, and RAS-family mutations. These driver
    events arise in thyroid follicular cells and establish the genotype-phenotype
    patterns that distinguish conventional papillary tumors from more
    follicular-patterned neoplasms.
  cell_types:
  - preferred_term: thyroid follicular cell
    term:
      id: CL:0002258
      label: thyroid follicular cell
  locations:
  - preferred_term: thyroid gland
    term:
      id: UBERON:0002046
      label: thyroid gland
  evidence:
  - reference: PMID:39502057
    reference_title: "[Correlations of Ultrasound Features With Gene Mutations and Pathologic Subtypes in Papillary Thyroid Carcinoma]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations."
    explanation: Supports the major early driver classes emphasized in papillary thyroid carcinoma.
  - reference: PMID:41175860
    reference_title: "Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations."
    explanation: Anchors the characterization of these driver events as the primary (early) molecular alterations in follicular-cell-derived thyroid tumors.
  downstream:
  - target: MAPK Pathway Hyperactivation
    description: Driver mutations and fusions converge on persistent mitogenic signaling
- name: MAPK Pathway Hyperactivation
  description: >-
    Driver alterations converge on chronic MAPK signaling, which promotes thyroid
    follicular cell proliferation and malignant transformation. BRAF-like tumors
    especially depend on this pathway and often show loss of thyroid
    differentiation programs relevant to iodine handling.
  biological_processes:
  - preferred_term: MAPK cascade
    modifier: INCREASED
    term:
      id: GO:0000165
      label: MAPK cascade
  evidence:
  - reference: PMID:41175860
    reference_title: "Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations."
    explanation: Supports the dominant BRAF-like and RAS-like molecular programs that organize papillary thyroid carcinoma biology.
  - reference: PMID:41368991
    reference_title: "BRAF V600E in thyroid cancer: navigating prognostic uncertainty and therapeutic opportunity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BRAF V600E, the most common oncogenic driver in papillary thyroid carcinoma, activates the MAPK pathway and suppresses genes involved in iodine metabolism and differentiation."
    explanation: Supports the role of BRAF-driven MAPK activation and reduced differentiation in a major papillary thyroid carcinoma subset.
  downstream:
  - target: Aggressive Progression and Reduced Differentiation
    description: Additional oncogenic hits superimposed on driver signaling promote dedifferentiation and treatment resistance
- name: Aggressive Progression and Reduced Differentiation
  description: >-
    A subset of papillary thyroid carcinomas acquires additional alterations such
    as TERT promoter mutation, TP53 disruption, and aberrant PI3K-PTEN-AKT
    signaling. These changes are associated with progression toward more
    aggressive, less-differentiated, and radioiodine-refractory disease.
  biological_processes:
  - preferred_term: phosphatidylinositol 3-kinase/protein kinase B signal transduction
    modifier: INCREASED
    term:
      id: GO:0043491
      label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
  - preferred_term: cell differentiation
    modifier: DECREASED
    term:
      id: GO:0030154
      label: cell differentiation
  evidence:
  - reference: PMID:41175860
    reference_title: "Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progression of thyroid tumors to advanced and less-differentiated carcinomas requires additional oncogenic alterations, including TP53 and TERT promoter mutation, and aberrant PI3K-PTEN-AKT signaling."
    explanation: Supports the progression model linking additional alterations to aggressive and less-differentiated thyroid carcinoma states.
histopathology:
- name: Papillary Thyroid Carcinoma
  finding_term:
    preferred_term: Thyroid Gland Papillary Carcinoma
    term:
      id: NCIT:C4035
      label: Thyroid Gland Papillary Carcinoma
  frequency: VERY_FREQUENT
  description: >-
    Papillary thyroid carcinoma is the dominant malignant thyroid histology and
    includes classical, follicular variant, tall cell, and other less common
    morphologic forms.
  evidence:
  - reference: PMID:21221869
    reference_title: "Papillary thyroid carcinoma variants."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies."
    explanation: Supports papillary thyroid carcinoma as the predominant malignant thyroid histology.
- name: Papillary-Type Nuclear Features
  frequency: VERY_FREQUENT
  diagnostic: true
  description: >-
    The hallmark diagnostic nuclear features of papillary thyroid carcinoma include
    nuclear enlargement with optically clear (ground-glass) chromatin ("Orphan-Annie
    eye" nuclei), longitudinal nuclear grooves, and intranuclear cytoplasmic
    pseudoinclusions. These papillary-type nuclear changes are required criteria for
    histological and cytological diagnosis, distinguishing PTC from benign follicular
    lesions. Their frequency correlates with BRAF V600E mutation in classical and
    tall-cell subtypes.
  evidence:
  - reference: PMID:26271724
    reference_title: "BRAF V600E and risk stratification of thyroid microcarcinoma: a multicenter pathological and clinical study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "nuclear grooves, optically clear nuclei, tall cells within the tumor"
    explanation: Multicenter pathological analysis of papillary thyroid microcarcinomas identifies nuclear grooves and optically clear nuclei as characteristic microscopic features correlated with BRAF V600E.
- name: Psammoma Bodies
  finding_term:
    preferred_term: psammoma body formation
    term:
      id: NCIT:C27709
      label: Psammoma Body Formation
  description: >-
    Psammoma bodies are concentrically laminated calcified structures that form
    by dystrophic calcification of infarcted papillae or necrotic neoplastic cells.
    They are a diagnostically useful but non-universal finding in papillary thyroid
    carcinoma. Although their sensitivity is low (they are absent in a substantial
    minority of PTCs), their presence is highly specific for malignancy and for PTC
    in particular, especially when encountered in cervical lymph node tissue.
    Identification of psammoma bodies alone in a cervical lymph node is considered
    evidence of metastatic PTC even when viable tumor cells are absent.
  notes: >-
    Psammoma bodies are sufficiently specific for PTC that their incidental
    finding in cervical lymph nodes warrants a diligent search for a primary
    papillary thyroid carcinoma. They are absent or sparse in follicular and
    anaplastic thyroid carcinoma.
  evidence:
  - reference: PMID:37181946
    reference_title: "The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%."
    explanation: Retrospective study of 337 PTC patients confirms psammoma bodies as perfectly specific for PTC on FNA cytology despite lower sensitivity, supporting their role as a high-value diagnostically specific feature.
phenotypes:
- category: Endocrine
  name: Thyroid Nodule
  diagnostic: true
  description: >-
    Most patients present with a thyroid nodule detected clinically or on
    imaging.
  phenotype_term:
    preferred_term: Thyroid nodule
    term:
      id: HP:0025388
      label: Thyroid nodule
  evidence:
  - reference: PMID:24276450
    reference_title: "The accuracy of thyroid nodule ultrasound to predict thyroid cancer: systematic review and meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common type of cancer was papillary thyroid cancer (84%)."
    explanation: In a meta-analysis of 18,288 thyroid nodules, papillary thyroid carcinoma was the predominant malignancy identified, consistent with the thyroid nodule being the characteristic presentation of papillary thyroid carcinoma.
- category: Systemic
  name: Cervical Lymphadenopathy
  description: >-
    Regional cervical lymph node involvement is common and may be present at
    diagnosis, particularly in younger patients and in tumors with higher-risk
    molecular or histologic features.
  phenotype_term:
    preferred_term: Lymphadenopathy
    term:
      id: HP:0002716
      label: Lymphadenopathy
  evidence:
  - reference: PMID:29329789
    reference_title: "Lateral lymph node metastasis in papillary thyroid carcinoma: A systematic review and meta-analysis for prevalence, risk factors, and location."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Lymph node metastasis (LNM) is frequent in papillary thyroid carcinoma (PTC) and is associated with a poor prognosis."
    explanation: Systematic review and meta-analysis supports regional lymph node metastasis as a frequent feature of papillary thyroid carcinoma.
biochemical:
- name: Thyroglobulin
  notes: >-
    Thyroglobulin remains a practical diagnostic and surveillance biomarker in
    differentiated thyroid cancer. Immunohistochemical staining is especially
    helpful in confirming papillary thyroid carcinoma at metastatic sites, and
    serum thyroglobulin is widely used for postoperative monitoring of disease
    recurrence after thyroidectomy.
  evidence:
  - reference: PMID:21221869
    reference_title: "Papillary thyroid carcinoma variants."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Immunohistochemical staining with TTF-1 and thyroglobulin is very useful in confirming the diagnosis of papillary thyroid carcinoma especially in metastatic sites."
    explanation: Supports the diagnostic utility of thyroglobulin immunostaining in papillary thyroid carcinoma at metastatic sites.
  - reference: PMID:26462967
    reference_title: "2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "surveillance for recurrent disease using imaging and serum thyroglobulin"
    explanation: ATA guidelines confirm serum thyroglobulin as a standard postoperative surveillance marker for differentiated thyroid cancer including PTC.
- name: Molecular Driver Testing
  notes: >-
    Molecular testing for BRAF V600E, RET/PTC rearrangements, and RAS-family
    mutations can refine prognostic assessment, clarify subtype biology, and
    guide targeted therapy discussions in advanced disease.
  evidence:
  - reference: PMID:39502057
    reference_title: "[Correlations of Ultrasound Features With Gene Mutations and Pathologic Subtypes in Papillary Thyroid Carcinoma]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The prognosis of papillary thyroid carcinoma (PTC) is highly dependent on gene mutations and pathologic features."
    explanation: Supports routine clinical relevance of molecular and pathologic stratification in papillary thyroid carcinoma.
genetic:
- name: BRAF
  gene_term:
    preferred_term: BRAF
    term:
      id: hgnc:1097
      label: BRAF
  association: Somatic Activating Mutations
  notes: >-
    BRAF V600E is the most common single driver alteration in conventional
    papillary thyroid carcinoma. It activates MAPK signaling and is associated
    with higher risk of nodal metastasis and recurrence in aggregate analyses.
    However, a large meta-analysis of 20,570 patients found no significant
    association with distant metastases (OR=0.75) or disease-specific mortality
    (OR=0.97), limiting its role as an independent prognostic marker for survival.
  evidence:
  - reference: PMID:41368991
    reference_title: "BRAF V600E in thyroid cancer: navigating prognostic uncertainty and therapeutic opportunity."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "BRAF V600E, the most common oncogenic driver in papillary thyroid carcinoma, activates the MAPK pathway and suppresses genes involved in iodine metabolism and differentiation."
    explanation: Supports BRAF V600E as the dominant papillary thyroid carcinoma driver and a mechanism for MAPK activation.
  - reference: PMID:41419184
    reference_title: "Prognostic Value of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis of Nodal Involvement, Distant Metastases, Recurrence, and Mortality."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Overall, these findings confirm that BRAF V600E mutation is associated with an increased risk of nodal metastasis and recurrence in papillary thyroid carcinoma."
    explanation: Supports the clinical association between BRAF V600E and adverse recurrence-related features.
  - reference: PMID:41419184
    reference_title: "Prognostic Value of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis of Nodal Involvement, Distant Metastases, Recurrence, and Mortality."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "However, its lack of impact on distant metastases and disease-specific mortality limits its role as an independent prognostic marker in clinical decision-making."
    explanation: The same meta-analysis found no significant association with distant metastases or disease-specific mortality, qualifying BRAF V600E as an incomplete independent prognostic marker.
- name: RET
  gene_term:
    preferred_term: RET
    term:
      id: hgnc:9967
      label: RET
  association: Somatic Gene Fusions
  notes: >-
    RET/PTC rearrangements define an important papillary thyroid carcinoma subset,
    especially in radiation-associated disease, and converge on the same
    mitogenic pathways as other canonical drivers.
  evidence:
  - reference: PMID:39502057
    reference_title: "[Correlations of Ultrasound Features With Gene Mutations and Pathologic Subtypes in Papillary Thyroid Carcinoma]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations."
    explanation: Supports RET/PTC rearrangements as one of the major recurrent driver classes in papillary thyroid carcinoma.
- name: RAS family genes
  association: Somatic Activating Mutations
  notes: >-
    RAS-family mutations are common in more follicular-patterned papillary thyroid
    carcinoma and related differentiated thyroid neoplasms, reflecting a RAS-like
    signaling program distinct from classical BRAF-like tumors.
  evidence:
  - reference: PMID:39502057
    reference_title: "[Correlations of Ultrasound Features With Gene Mutations and Pathologic Subtypes in Papillary Thyroid Carcinoma]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The common gene mutations in PTC include BRAF V600E,RET/PTC rearrangement,and RAS mutations."
    explanation: Supports RAS-family alterations as recurrent papillary thyroid carcinoma drivers.
  - reference: PMID:41175860
    reference_title: "Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In most tumors of follicular cell origin, the primary molecular events are RAS or RAS-like (follicular-patterned tumors) and BRAF p.V600E or BRAF V600E-like (conventional papillary carcinomas) alterations."
    explanation: Supports the distinction between RAS-like follicular-patterned tumors and BRAF-like conventional papillary carcinomas.
- name: TERT
  gene_term:
    preferred_term: TERT
    term:
      id: hgnc:11730
      label: TERT
  association: Somatic Promoter Mutations
  notes: >-
    TERT promoter mutations are progression-associated events linked to aggressive,
    less-differentiated, and radioiodine-refractory thyroid carcinoma states.
  evidence:
  - reference: PMID:41175860
    reference_title: "Somatic genetic alterations in the development and progression in thyroid tumors of follicular cells."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Progression of thyroid tumors to advanced and less-differentiated carcinomas requires additional oncogenic alterations, including TP53 and TERT promoter mutation, and aberrant PI3K-PTEN-AKT signaling."
    explanation: Supports TERT promoter mutation as a late progression event in aggressive thyroid carcinoma biology.
environmental:
- name: Ionizing Radiation Exposure
  exposure_term:
    preferred_term: exposure to ionizing radiation
    term:
      id: ECTO:7000047
      label: exposure to ionizing radiation
  influences_mechanisms:
  - target: Driver Alterations in Thyroid Follicular Cells
    environmental_effect: TRIGGERS
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Radiation reaching the thyroid causes double-strand breaks whose
      mis-joining produces the rearrangement-type drivers characteristic of
      radiation-associated disease, so the exposure reaches this node through
      a known repair-error step.
    evidence:
    - reference: PMID:21221869
      reference_title: "Papillary thyroid carcinoma variants."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The most common etiologic factor is radiation"
      explanation: >-
        Identifies radiation as the most common etiologic factor for this
        cancer, the exposure that generates its driver alterations.
  notes: >-
    Ionizing radiation is the strongest established environmental risk factor for
    papillary thyroid carcinoma, especially after childhood or adolescent exposure.
  evidence:
  - reference: PMID:21221869
    reference_title: "Papillary thyroid carcinoma variants."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common etiologic factor is radiation"
    explanation: Supports radiation exposure as the leading established environmental risk factor for papillary thyroid carcinoma.
treatments:
- name: Thyroidectomy
  description: >-
    Surgical resection is the mainstay of treatment for localized papillary
    thyroid carcinoma.
  treatment_term:
    preferred_term: Thyroidectomy
    term:
      id: NCIT:C51648
      label: Thyroidectomy
- name: Radioiodine Therapy
  description: >-
    Radioactive iodine is used selectively after surgery for intermediate-risk,
    high-risk, or metastatic differentiated thyroid cancer.
  treatment_term:
    preferred_term: Radioactive Iodine Therapy
    term:
      id: NCIT:C157968
      label: Radioactive Iodine Therapy
- name: Mutation-Directed Targeted Therapy
  description: >-
    Advanced papillary thyroid carcinoma with actionable driver alterations may
    be treated with genotype-matched targeted therapy, including RET inhibitors
    for RET fusion-positive disease and BRAF-directed regimens in BRAF V600E-
    driven refractory tumors.
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
- name: Lenvatinib or Sorafenib
  description: >-
    Multi-kinase inhibitors are standard systemic options for progressive
    radioiodine-refractory differentiated thyroid cancer when surgery and
    radioiodine are no longer sufficient.
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
    therapeutic_agent:
    - preferred_term: lenvatinib
      term:
        id: CHEBI:85994
        label: lenvatinib
    - preferred_term: sorafenib
      term:
        id: CHEBI:50924
        label: sorafenib
- name: Cabozantinib
  description: >-
    Cabozantinib is a multi-kinase inhibitor (VEGFR2, MET, AXL, RET) used in the
    second-line setting for radioiodine-refractory differentiated thyroid cancer
    that has progressed during or after lenvatinib or sorafenib. This
    VEGFR-TKI-refractory population previously had no standard of care; the
    randomised placebo-controlled COSMIC-311 trial met its progression-free
    survival endpoint at interim analysis, at the cost of substantially more
    grade 3-4 toxicity (palmar-plantar erythrodysaesthesia, hypertension,
    fatigue).
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: targeted therapy
    term:
      id: NCIT:C93352
      label: Targeted Therapy
    therapeutic_agent:
    - preferred_term: cabozantinib
      term:
        id: CHEBI:72317
        label: cabozantinib
  evidence:
  - reference: PMID:34237250
    reference_title: "Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients must have received previous lenvatinib or sorafenib and progressed during or after treatment with up to two VEGFR tyrosine kinase inhibitors."
    explanation: Defines the second-line, VEGFR-TKI-refractory population in which cabozantinib was evaluated, downstream of the lenvatinib/sorafenib option already curated here.
  - reference: PMID:34237250
    reference_title: "Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cabozantinib showed significant improvement in progression-free survival over placebo: median not reached ... versus 1·9 months (1·8-3·6); hazard ratio 0·22 (96% CI 0·13-0·36; p<0·0001)"
    explanation: Reports the randomised progression-free survival benefit that supports cabozantinib as an active option after VEGFR-TKI failure.
  - reference: PMID:34237250
    reference_title: "Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Grade 3 or 4 adverse events occurred in 71 (57%) of 125 patients receiving cabozantinib and 16 (26%) of 62 receiving placebo"
    explanation: Quantifies the grade 3-4 toxicity burden stated in the description, so the efficacy claim is not curated without its safety cost.
  - reference: PPR:PPR1274359
    reference_title: "Efficacy, Safety, and Certainty of Evidence for Systemic Antineoplastic Therapies in Treatment-resistant Adult Malignancies: A Systematic Review, Exploratory Meta-analysis, and Grade Assessment"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cabozantinib contributed high-certainty evidence for progression-free survival in radioiodine-refractory differentiated thyroid cancer after previous VEGFR-targeted therapy"
    explanation: >-
      GRADE certainty rating from a 2026 systematic review of treatment-resistant
      malignancies, corroborating (not solely supporting) the COSMIC-311 result
      above. Non-peer-reviewed preprint; cited only alongside the peer-reviewed
      trial report.
clinical_trials:
- name: NCT03690388
  phase: PHASE_III
  status: ACTIVE_NOT_RECRUITING
  description: >-
    COSMIC-311: randomised, double-blind, placebo-controlled phase 3 trial of
    cabozantinib in radioiodine-refractory differentiated thyroid cancer
    (papillary or follicular and their variants) progressing after prior
    VEGFR-targeted therapy. Primary endpoints were objective response rate and
    progression-free survival.
  evidence:
  - reference: clinicaltrials:NCT03690388
    reference_title: "A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Cabozantinib (XL184) in Subjects With Radioiodine-Refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      evaluate the effect of cabozantinib compared with placebo on progression
      free survival (PFS) and objective response rate (ORR) in subjects with
      Radioiodine-Refractory Differentiated Thyroid Cancer (DTC) who have
      progressed after prior vascular endothelial growth factor receptor
      (VEGFR)-Targeted therapy
    explanation: The registered trial objective matches the second-line indication curated in the Cabozantinib treatment entry.
  notes: >-
    ClinicalTrials.gov API status checked 2026-08-16 reported
    ACTIVE_NOT_RECRUITING. Primary results are reported in PMID:34237250, cited
    on the Cabozantinib treatment entry.
prevalence:
- population: Worldwide
  measure_type: ANNUAL_INCIDENCE
  prevalence_class: COMMON
  notes: >-
    Papillary thyroid carcinoma is the most common thyroid malignancy, constituting
    more than 70% of all thyroid cancers. Global incidence has been rising substantially
    over recent decades, driven in part by increased use of thyroid ultrasound and
    detection of small, clinically occult tumors. Incidence varies markedly by region,
    with higher rates in countries with widespread thyroid imaging programs (e.g., the
    United States, South Korea) and lower rates in lower-resource settings. Note: this
    entry shares MONDO:0005075 with the BRAF_Mutant_Thyroid_Cancer and
    RET_Fusion_Thyroid_Cancer molecular-subtype sibling entries; these subtypes
    collectively represent a large proportion of the overall PTC incidence.
  evidence:
  - reference: PMID:21221869
    reference_title: "Papillary thyroid carcinoma variants."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Papillary thyroid carcinomas are the most common thyroid cancers and constitute more than 70% of thyroid malignancies."
    explanation: Establishes PTC as the dominant thyroid cancer histotype comprising over 70% of all thyroid malignancies.
  - reference: PMID:26462967
    reference_title: "2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "differentiated thyroid cancer is becoming increasingly prevalent"
    explanation: ATA 2015 guidelines acknowledge the rising incidence of differentiated thyroid cancer (predominantly PTC).
disease_term:
  preferred_term: papillary thyroid carcinoma
  term:
    id: MONDO:0005075
    label: thyroid gland papillary carcinoma
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0005075
      label: thyroid gland papillary carcinoma
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: MONDO provides an exact disease term for papillary thyroid carcinoma; this is the same term used as `disease_term` for this entry.
  ncit_mappings:
  - term:
      id: NCIT:C4035
      label: Thyroid Gland Papillary Carcinoma
    mapping_predicate: skos:exactMatch
    mapping_source: NCIT
    mapping_justification: NCIT provides an exact neoplasm term for papillary thyroid carcinoma; cross-referenced from MONDO:0005075.

classifications:
  icdo_morphology:
    classification_value: Carcinoma
  harrisons_chapter:
  - classification_value: ONCOLOGY_HEMATOLOGY
datasets:
- accession: ega:EGAS00001001268
  title: Whole exome sequencing of papillary thyroid carcinoma in the Chinese population
  description: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Here we submitted the sequencing results for PTC using 91 tumor-normal pairs through exome sequencing in the Chinese Han population.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Papillary Thyroid Carcinoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001004101
  title: The genomic landscape of metastatic papillary thyroid carcinoma and novel biomarkers for predicting distant metastasis
  description: Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland with arelatively high cure rate. Distant metastasis (DM) of PTC is uncommon, but when it occurs, itsignificantly decreases the survival of PTC patients. However, the molecular mechanisms of DMin PTCs have not been systematically studied. We performed whole exome sequencing andGeneseeqPrime (425 genes) panel sequencing of the primary tumor, plasma and matched whiteblood cell samples from 20 PTCs with DM and 46 PTCs without DM. We identified somaticmutations, gene fusions and copy number alterations and analyzed their relationships with DM ofPTCs.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Papillary Thyroid Carcinoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'
- accession: ega:EGAS00001005182
  title: Pediatric Papillary Thyroid Carcinoma RNA-Seq
  description: Papillary thyroid carcinoma (PTC) is the most common malignancy amongst adolescent and young adult women. Clinical and genomic features of PTC in children differ from those in adults. Historically, a substantial proportion (~50%) of pediatric PTC (PPTC) lack any of the common driver mutations typical of adult PTC. Thus, molecular diagnostics developed for adults may not be valid in children. We applied novel bioinformatic pipelines to RNASeq analysis of pediatric thyroid tumors to identify known and novel fusion oncogenes as drivers of tumorigenesis and to define gene expression patterns among tumors.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  notes: 'European Genome-phenome Archive study, matched because the disease is named in the study''s own title ("Papillary Thyroid Carcinoma"); description-level mentions were not accepted. EGA study_type: Other. Controlled access -- data require a Data Access Agreement. EGA metadata retrieved 2026-08-01.'

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Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Papillary Thyroid Carcinoma. Core disease mechanisms, molecular and cellul...

Asta Scientific Corpus Retrieval 19 citations 2026-04-11T22:18:09.935792

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Papillary Thyroid Carcinoma. Core disease mechanisms, molecular and cellul...

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

Papers retrieved: 19
Snippets retrieved: 20

Relevant Papers

[1] Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer

Authors: M. G. de Matos, Mafalda Pinto, A. Gonçalves, Sule Canberk, M. J. Bugalho et al.
Year: 2025
Venue: PeerJ
URL: https://www.semanticscholar.org/paper/655de68f1a7e8137dcba8a2046f14dee4f07594d
DOI: 10.7717/peerj.18801
PMID: 39850836
PMCID: 11756370
Citations: 4
Summary: The knowledge of genetic and molecular biomarkers has achieved a high level of complexity, and the difficulties related to its applicability determine that their implementation in clinical practice is not yet a reality.
Evidence snippets:
Snippet 1 (score: 0.617) > Knowledge of molecular mechanisms implicated in thyroid carcinogenesis has been attained in recent years. Thyroid neoplasm result from alterations in gene expression patterns, which occur due to a gradual accumulation of genetic and epigenetic events. These changes are associated with specific tumor phenotypes and are implicated in disease etiology. Molecular alterations induce the activation of different signaling pathways, such as the mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K/AKT/mTOR), which are involved in and promote carcinogenesis (Hsiao & Nikiforov, 2014). In a few years, the knowledge of molecular mechanisms implicated in thyroid carcinogenesis changed from understanding signaling pathways and identification of a few genes mutations to the knowledge of the main genes implicated in thyroid carcinogenesis, reviewed by De Leo et al. (2024). Genetic changes in thyroid neoplasms were divided in early/driver molecular alterations and late/progression events. Late/ progression events may be associated with early/driver molecular alterations and represent the evolution from well-differentiated to high-grade and undifferentiated carcinoma, being (Pozdeyev et al., 2018). Most frequent gene mutations present in follicular-cell derived thyroid tumors are BRAF, RAS, and TERTp mutations, associate with clinically relevant clinicopathologic features, as shown in Table 3.

[2] Redox metabolism correlates with cellular turnover and clinical phenotype of papillary thyroid carcinoma and colloid goiter

Authors: B. Rovčanin, K. Gopčević, D. Kekic, V. Živaljević, A. Diklic et al.
Year: 2019
Venue: Archives of Medical Science : AMS
URL: https://www.semanticscholar.org/paper/acbf6d9a1f376505739b57296f151bed9e8a8373
DOI: 10.5114/aoms.2019.88374
PMID: 36160341
PMCID: 9479590
Citations: 1
Summary: PTC tissue is characterized by increased antioxidant activity and a normal prooxidation level, and AOPP is the most powerful predictor of PTC capsular invasion, multicentric intrathyroid dissemination and lymph node metastasis phenotype.
Evidence snippets:
Snippet 1 (score: 0.569) > Thyroid neoplasms represent the most common endocrine malignancy, with an increasing incidence over the past decades. Papillary thyroid car-cinoma (PTC) is a well-differentiated thyroid carcinoma, which contributes to approximately 80% of all thyroid malignancies [1]. PTC is frequently multifocal and it usually metastasizes in regional neck lymph nodes while distant metastases are very rare [2]. The clinical course of PTC is benevolent in most patients, as testified by the 90% 5-year survival rate, while the other 10% of patients develop recurrent disease and aggressive clinical progression [3]. Taking into account the frequency of PTC and its clinical importance, it is essential to gain better understanding of its carcinogenesis process. Substantial progress in PTC's molecular pathogenesis has been achieved, on the basis of biochemical, genetic and omics studies. These studies showed the importance of the mitogen-activated protein kinases (MAPK) and phosphatidylinositol 3-kinases-protein kinase B (PI3K-AKT) signaling pathways, whose activation is considered the primary oncogenic event in PTC carcinogenesis, as well as in other pathological states [4,5]. Genetic modifications that account for alterations of these pathways include point mutations, major rearrangements, copy-number variants and changes in gene methylation [6]. In a complex cellular signaling network these two pathways contribute to the regulation of proliferation and apoptosis as well as the redox status, which has a crucial influence on cell survival [7]. Oxidative stress takes place when the large number of generated reactive oxygen species (ROS) cannot be scavenged by cellular antioxidative mechanisms. This state leads to the damage of lipids, proteins and DNA, compromising normal cellular functioning and survival [8]. The extent of oxidative stress is estimated by quantification of biomarkers such as malondialdehyde (MDA) as a marker of lipid peroxidation, advanced oxidation protein products (AOPP) as a marker of oxidative protein damage and 8-oxo-2′-deoxyguanosine (8-oxo-d

[3] Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma

Authors: Medi Kori, Kubra Temiz, E. Gov
Year: 2023
Venue: Journal of Cellular and Molecular Medicine
URL: https://www.semanticscholar.org/paper/94a4aeba681311c594a691c2cd4845397410a4c9
DOI: 10.1111/jcmm.18002
PMID: 37859510
PMCID: 10746936
Citations: 7
Summary: The need for differential co‐expression analysis to gain a systems‐level understanding of a complex disease is highlighted, and a candidate prognostic systems biomarker and novel drugs for PTC are provided.
Evidence snippets:
Snippet 1 (score: 0.529) > Recent cancer statistics show that thyroid cancer is the most common endocrine cancer encountered by mankind. In 2022, it was estimated that 43,800 patients were diagnosed with thyroid cancer, and thyroid cancer was responsible for 2230 deaths in the United States. 1 Papillary, follicular, medullary, and undifferentiated or anaplastic thyroid carcinomas are the major histologic groups of thyroid tumours. Among the various subgroups of thyroid cancer, papillary thyroid carcinoma (PTC) accounts for the largest proportion of all thyroid carcinomas. Notably, the prevalence of PTC is approximately 85% when all thyroid carcinomas are considered. 2 e aetiology of thyroid cancer is not well understood. Therefore, further studies are needed to uncover the underlying mechanisms of the disease, correct over-diagnosis, and find prognostic and/or drug candidates to reduce the prevalence of PTC. > Logarithmic advances in high-throughput sequencing and screening methods in recent decades have produced a substantial amount of X-ome data at various molecular levels, enabling researchers to perform various bioinformatics approaches for different diseases 3,4 and also for PTC. 5 However, some of these studies take only limited account of the reality of the molecular biochemistry of the organism. To discover specific disease biomarkers or drug targets, it is essential to evaluate the entire physical and functional architecture of the organism, because the development of an abnormal phenotype (i.e. disease) is not the result of a single gene, but rather the result of complex gene interactions. One scientific field, network medicine, allows researchers to uncover these complex interactions between biomolecules of a given phenotype in a holistic view. 6 ne and protein networks provide valuable data for molecular interactions within the organism, and co-expression networks represent significantly co-regulated groups of genes (i.e. modules). Any differentiation in gene correlations between different phenotypes can provide clues to the phenotype and supports the discovery of systems biomarkers. 7 To reveal co-expression relationships among genes in thyroid cancer, weighted gene co-expression network analysis (WGCNA) has been performed in a limited number of studies. 8,9 WGCNA identifies gene modules by hierarchical clustering.

[4] In silico Analysis of Publicly Available Transcriptomics Data Identifies Putative Prognostic and Therapeutic Molecular Targets for Papillary Thyroid Carcinoma

Authors: A. Almansoori, P. Bhamidimarri, R. Bendardaf, R. Hamoudi
Year: 2022
Venue: International Journal of General Medicine
URL: https://www.semanticscholar.org/paper/6de2046cc1bb187ea53cf5ceef550ba1a4e2b969
DOI: 10.2147/IJGM.S345336
PMID: 35330879
PMCID: 8939872
Citations: 4
Summary: Background Thyroid cancer is the most common endocrine malignancy. However, the molecular mechanism involved in its pathogenesis is not well characterized. Purpose The objective of this study is to identify key cellular pathways and differentially expressed genes along the thyroid cancer pathogenesis sequence as well as to identify potential prognostic and therapeutic targets. Methods Publicly available transcriptomics data comprising a total of 95 samples consisting of 41 normal, 28 non-aggr...
Evidence snippets:
Snippet 1 (score: 0.517) > Background Thyroid cancer is the most common endocrine malignancy. However, the molecular mechanism involved in its pathogenesis is not well characterized. Purpose The objective of this study is to identify key cellular pathways and differentially expressed genes along the thyroid cancer pathogenesis sequence as well as to identify potential prognostic and therapeutic targets. Methods Publicly available transcriptomics data comprising a total of 95 samples consisting of 41 normal, 28 non-aggressive and 26 metastatic papillary thyroid carcinoma (PTC) cases were used. Transcriptomics data were normalized and filtered identifying 9394 differentially expressed genes. The genes identified were subjected to pathway analysis using absGSEA identifying PTC related pathways. Three of the genes identified were validated on 508 thyroid cancer biopsies using RNAseq and TNMplot. Results Pathway analysis revealed a total of 2193 differential pathways among non-aggressive samples and 1969 among metastatic samples compared to normal tissue. Pathways for non-aggressive PTC include calcium and potassium ion transport, hormone signaling, protein tyrosine phosphatase activity and protein tyrosine kinase activity. Metastatic pathways include growth, apoptosis, activation of MAPK and regulation of serine threonine kinase activity. Genes for non-aggressive are KCNQ1, CACNA1D, KCNN4, BCL2, and PTK2B and metastatic PTC are EGFR, PTK2B, KCNN4 and BCL2. Three of the genes identified were validated using clinical biopsies showing significant overexpression in aggressive compared to non-aggressive PTC; EGFR (p < 0.05), KCNN4 (p < 0.001) and PTK2B (p < 0.001). DrugBank database search identified several FDA approved drug targets including anti-EGFR Vandetanib used to treat thyroid cancer in addition to others that may prove useful in treating PTC. Conclusion Transcriptomics analysis identified putative prognostic targets including EGFR, PTK2B, BCL2, KCNQ1, KCNN4 and CACNA1D. EGFR, PTK2B and KCN44 were validated using thyroid cancer clinical biopsies. The drug search identified FDA approved drugs including
Snippet 2 (score: 0.509) > Thyroid cancer was ranked as the most common endocrine malignancy. 1 Globally, thyroid cancer incidence has been on the rise over the past three decades. Between 2006 and 2012, the annual incidence rate was 6.5% in women and 5.4 in men. 2,3 In the United States between 2000 and 2009, thyroid cancer incidence rate was the highest among all cancers. 4 The mortality rate of thyroid cancer is considered to be low, whilst the reoccurrence and persistence of the disease is still considered high. 5 Morphologically, thyroid cancers are classified into different cellular subtypes such as papillary, follicular, medullary and anaplastic. Differentiated papillary thyroid carcinoma (PTC) form is the most common type comprising more than 80% of all thyroid cases as shown in Table 1. Genetic mutations have been associated with PTC. 6 Whilst many genomic mutational screening studies were carried out on thyroid cancer in general and PTC in particular, only few have identified mutated genes that are correlated with progression of PTC including TP53 and KRAS/BRAF 7 . However, although such studies suggested that thyroid cancer has high degree of intra-tumoral heterogeneity, 8 the mutations identified did not provide clear insights into the molecular mechanism of thyroid cancer phenotypes and progression. Thus, for better clinical outcomes, there is a compelling need to actively study alterations in cellular pathways linked to the underlying mechanism of thyroid cancer initiation and progression. > Few transcriptomic analyses were carried out on PTC identifying some of the cellular pathways involved in its pathogenesis 9 . However, such studies were generally carried out on small number of patients using standard bioinformatics analysis focusing on list of differentially expressed genes. This provided limited insights into the molecular basis of PTC without clear association to diagnostic, prognostic and therapeutic targets. > In this study, we carried out comprehensive and systematic in silico pathway analysis of PTC using in-house bioinformatics pipeline that has shown good ability to identify the transcriptomic profiles and related differentially expressed genes between different subtypes of the same disease. 10 The aim of this study is to attempt to identify the key transcriptomic signatures that drive non-aggressive and metastatic PTC as well as using such signature to identify putative drug targets

[5] Systems biology approach delineates critical pathways associated with papillary thyroid cancer: a multi-omics data analysis

Authors: Febby Payva, Santhy K. S., Remya James, Amrisa Pavithra E, Venketesh Sivaramakrishnan
Year: 2025
Venue: Thyroid Research
URL: https://www.semanticscholar.org/paper/73aae1bf968c7f2bd94ee5aae5bbe4dd480c8a86
DOI: 10.1186/s13044-025-00230-1
PMID: 40211357
PMCID: 11987294
Summary: Papillary thyroid cancer (PTC) is the most prevalent follicular cell-derived subtype of thyroid cancer. A systems biology approach to PTC can elucidate the mechanism by which molecular components work and interact with one another to decipher a panoramic view of the pathophysiology. PTC associated genes and transcriptomic data were retrieved from DisGeNET and Gene Expression Omnibus database respectively. Published proteomic and metabolomic datasets in PTC from EMBL-EBI were used. Gene Ontolo...
Evidence snippets:
Snippet 1 (score: 0.496) > Papillary thyroid cancer (PTC) is the most prevalent follicular cell-derived subtype of thyroid cancer. A systems biology approach to PTC can elucidate the mechanism by which molecular components work and interact with one another to decipher a panoramic view of the pathophysiology. PTC associated genes and transcriptomic data were retrieved from DisGeNET and Gene Expression Omnibus database respectively. Published proteomic and metabolomic datasets in PTC from EMBL-EBI were used. Gene Ontology and pathway analyses were performed with SNPs, differentially expressed genes (DEGs), proteins, and metabolites linked to PTC. The effect of a nucleotide substitution on a protein's function was investigated. Additionally, significant transcription factors (TFs) and kinases were identified. An integrated strategy was used to analyse the multi-omics data to determine the key deregulated pathways in PTC carcinogenesis. Pathways linked to carbohydrate, protein, and lipid metabolism, along with the immune response, signaling, apoptosis, gene expression, epithelial–mesenchymal transition (EMT), and disease onset, were identified as significant for the clinical and functional aspects of PTC. Glyoxylate and dicarboxylate metabolism and citrate cycle were the most common pathways among the PTC omics datasets. Commonality analysis deciphered five TFs and fifty-seven kinases crucial for PTC genesis and progression. Core deregulated pathways, TFs, and kinases modulate critical biological processes like proliferation, angiogenesis, immune infiltration, invasion, autophagy, EMT, and metastasis in PTC. Identified dysregulated pathways, TFs and kinases are critical in PTC and may help in systems level understanding and device specific experiments, biomarkers, and drug targets for better management of PTC.

[6] Association of CYP2D6*4 gene polymorphism with early papillary thyroid carcinoma

Authors: Aynur Dağlar Aday, T. Öztürk, Başak Akadam Teker, F. Aksoy, H. Aydogan et al.
Year: 2021
Venue: Turkish Journal of Biochemistry
URL: https://www.semanticscholar.org/paper/db3c0cf5196ebfc63ae9fafe575afc3ad519f7c0
DOI: 10.1515/tjb-2020-0103
Citations: 2
Summary: The findings indicate that the poor metabolizer CYP2D6*4 genotype may be a risk factor, especially in early PTC development.
Evidence snippets:
Snippet 1 (score: 0.491) > Although thyroid carcinomas constitute only 1% of all malignancies in humans; they are responsible for more than 90% of all endocrine cancers [1]. The majority of thyroid cancers are epithelial tumors that arise from thyroid follicular cells. They are mainly classified into three subtypes: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC) and anaplastic thyroid carcinoma (ATC). Differently, medullary thyroid carcinoma (MTC) derives from thyroid parafollicular (C) cells [2]. > PTC, the commonest type of endocrine malignancy, is a differentiated cancer and its incidence has risen a lot in recent decades [3]. PTC is classified into three major variants. Those are classic (CVPTC), follicular (FVPTC) and tall cell variants (TCVPTC). The genetic alterations of the signaling proteins in the mitogen-activated protein kinase (MAPK) pathway, including RET, ALK, RAS and BRAF are closely related with PTC [4]. Many additional tests used together with thyroid specimens have focused on biomarkers in this signaling pathway [5]. Although more advanced molecular tests are convenient, BRAF mutation is the most crucial biomarker for the diagnosis of PTC [6]. The molecular mechanisms that participate in PTC tumorigenesis and progression are not fully understood. Thus, elucidation of the underlying molecular mechanisms will be useful for the advancement of new diagnosis and treatment strategies for PTC. > Cytochrome P450s (CYPs) are mostly located in the liver and metabolize xenobiotics to non-toxic or carcinogenic metabolites [7]. CYP2D6 (debrisoquine hydroxylase) is a member of CYP family and the CYP2D6 gene takes place on chromosome 22q13.1 [8]. CYP2D6, takes part in the metabolism of drugs and bioactivation of several procarcinogens and neurotoxins [9].

[7] Identification of Hub Genes in Anaplastic Thyroid Carcinoma: Evidence From Bioinformatics Analysis

Authors: Liqi Li, Mingjie Zhu, Hu Huang, Junqiang Wu, D. Meng
Year: 2020
Venue: Technology in Cancer Research & Treatment
URL: https://www.semanticscholar.org/paper/080dbb6867eca7b73ad5b6e5accb4e2bdcdae280
DOI: 10.1177/1533033820962135
PMID: 33025856
PMCID: 7545761
Citations: 10
Summary: Several key genes are identified that may play key roles in ATC development and could serve as prognostic biomarkers or therapeutic targets and provide novel insights into the understanding of the molecular mechanisms of A TC development.
Evidence snippets:
Snippet 1 (score: 0.490) > 3][4] ATC arises from the follicular cells of the thyroid gland. However, compared to papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), ATC cells do not retain any of the biological features of normal follicular cells. 5 Clinically, ATC is characterized by aggressive local disease, high rates of metastasis, and extremely high mortality. 6,7 ased on this, there is an urgent need to further understand the unique biology and pathogenesis underlying this life-threatening disease. > During the last few decades, the clinical and molecular heterogeneity of ATC has been widely recognized, and much effort has been devoted to elucidating the mechanisms underlying this disease. To date, an increasing number of studies have suggested that the tumorigenesis of ATC is a stepwise dedifferentiation that involves the accumulation of somatic pro-carcinogenic mutations in genes such as TP53 and those involved in the PI3K-AKT-mTOR pathway 8,9 ; it has been widely established that BRAF V600E and RAS mutations are common drivers of this disease. 10,11 The current accepted hypothesis is that ATCs are driven from papillary thyroid carcinomas through the acquisition of a discrete number of genomic alterations. 12,13 8][19][20] Although many important drivers have been discovered through genomic and transcriptomic studies, the molecular mechanisms underlying ATC have still not been fully elucidated. > Based on this, we performed a series of bioinformatics analyses in an attempt to identify differentially expressed genes (DEGs) in ATC that are distinct from those in normal thyroid samples by analyzing datasets that were obtained from the Gene Expression Omnibus (GEO) database; we also explored the potential bio-functions through the use of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Furthermore, a protein-protein interaction (PPI) network was constructed, and 7 hub genes were identified based on this network. The results of our present study may provide new insights into the understanding of the molecular mechanisms of ATC development.

[8] Identification of Differentially Expressed Kinase and Screening Potential Anticancer Drugs in Papillary Thyroid Carcinoma

Authors: Huairong Zhang, B. Gao, B. Shi
Year: 2016
Venue: Disease Markers
URL: https://www.semanticscholar.org/paper/d6ea4f8f45c27aec5e4517c5a9390fe2315dd1fe
DOI: 10.1155/2016/2832980
PMID: 27703281
PMCID: 5040815
Citations: 4
Influential citations: 1
Summary: SRC, MAPK, and EGFR were the most important differentially expressed kinases in PTC and combined inhibitors may have high efficacy in P TC treatment by targeting these kinases.
Evidence snippets:
Snippet 1 (score: 0.485) > It is protein kinases that function as core in signaling pathways participating in tumor proliferation, invasion, metastasis, and tumor microenvironment formation in major types of tumors, including thyroid cancer pathogenesis. > It has been identified that in papillary thyroid carcinoma several molecular changes exist: rearranged during transfection (RET)/papillary thyroid carcinoma gene rearrangements, BRAF (B-RAF protooncogene, serine/threonine kinase) gene mutations, RAS (rat sarcoma) mutations, and vascular endothelial growth factor receptor 2 angiogenesis 2 Disease Markers pathways activation. BRAF oncogene mutation occurred in approximately 45% to 70% of patients with papillary thyroid carcinoma and VEGF overexpression is frequently found in tumors that originated in the thyroid [8][9][10][11]. In the landmark DECISION study, Sorafenib, a multikinase inhibitor of RET/RAS/RAF pathway, VEGF receptors 2 and 3, improved the progression-free survival by 3 months, from 5.8 months to 10.8 months, compared with placebo [12]. It emerged as a potentially effective option and approved by Food and Drug Administration (FDA) as a receptor tyrosine kinase inhibitor as treatment of differentiated thyroid cancer refractory to RAI. > We aimed to investigate the protein kinase expression difference between papillary thyroid carcinoma and normal thyroid and possible molecular mechanisms underlying PTC. We try to provide valuable information on PTC associated protein kinases for potential therapeutic targets.

[9] Identification of genes associated with lymph node metastasis in papillary thyroid carcinoma by weighted gene co-expression network analysis

Authors: Zhen Liu, Mingyue Guo, Lidong Wang, Chenxi Liu, Yongliang Huang
Year: 2020
Venue: Unknown venue
URL: https://www.semanticscholar.org/paper/9bd1ef8de46a1fde714e0e281dd9604b8d8b27cb
DOI: 10.21203/rs.2.23820/v1
Summary: The differential genes are screened by combining the datasets of TCGA, GEO and Oncomine in TC for the first time, which makes the screened differential genes have more biological significance.
Evidence snippets:
Snippet 1 (score: 0.484) > Thyroid cancer (TC) is a very frequent endocrine system malignant tumor. In recent years, its incidence is increasing year by year, and is generally younger [1]. The most common histological and pathological classification of TC is papillary thyroid carcinoma (PTC), accounting for 80% of all TC [2]. > However, although the growth of PTC is slow and most of the patients is a real good prognosis, there will be some patients with poor surgical results and insensitive to drug treatment, resulting in recurrence or metastasis or even death [3]. Researchers use genetic analysis to study the molecular mechanism of TC to explore the process of TC transfer. In the course of continuous exploration, many new genes related to the TC have been found [4][5][6]. However, at present, the understanding of the molecular mechanism of PTC is not certain. Despite the fact that many genes have clearly played an important role in the occurrence and development of PTC, cancer metastasis is a complex process, which is the result of the interaction of multiple genes. For example, mutation activation of Ras gene is the most classical gene mutation in TC. Because Ras gene is closely related to the classical signal pathway-PI3K/Akt signal pathway, it controls many cellular processes, such as cell growth, proliferation and survival, cell metabolism and autophagy [7]. The mutations of BRAF, RAS and RET-PTC fusion genes in the activated state can cause the activation of MAPK signal pathway, and the activation of p38MAPK/ERK signal transduction pathway will lead to cell proliferation and increase the apoptosis, autophagy and invasion of TC cells [8]. The study of the interaction between genes is more helpful for us to continue to explore the molecular mechanism of PTC. > Weighted co-expression network analysis (WGCNA) is a systems biology method used to describe gene association patterns among different samples. It can be used to establish highly synergistic gene sets, and to identify candidate biomarker genes or therapeutic targets according to the interconnectedness of gene sets and the association between gene sets and phenotypes.

[10] Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice

Authors: E. Tirrò, F. Martorana, Chiara Romano, S. Vitale, G. Motta et al.
Year: 2019
Venue: Genes
URL: https://www.semanticscholar.org/paper/d1ff1d9e8131c2446837add86af2de83c66ef8f6
DOI: 10.3390/genes10090709
PMID: 31540307
PMCID: 6771012
Citations: 87
Influential citations: 6
Summary: The genomic alterations and biological processes intertwined with thyroid cancer development are described, also providing a thorough overview of targeted drugs already tested or under investigation for these tumors.
Evidence snippets:
Snippet 1 (score: 0.484) > As thyroid cancer progresses, the accumulation of molecular alterations disrupting multiple normal cell functions results in RAIR development, due to impaired NIS expression [23][24][25].Indeed, dysregulation of different receptor-tyrosine kinase (RTK)-dependent signaling and proliferation pathways-such as the mitogen-activated protein kinase (MAPK), the phosphoinositide 3 kinase (PI3K), the Wingless/Integrated (WNT), the p53 and p73 pathways-are involved in the multistep tumorigenic process of thyroid cancer [25][26][27] (Figure 1).Alterations of these cascades can be linked to different mechanisms, including genetic and epigenetic modifications in pathway receptors and effectors [28,29].Moreover, distinct, mutually exclusive molecular alterations may be associated with specific disease stages or histotypes [30]. > Figure 1.Genetic events involved in thyroid carcinogenesis.Papillary thyroid carcinomas (PTC), follicular thyroid carcinomas (FTC) and anaplastic thyroid carcinomas (ATC) originate from thyroid follicular cells and are characterized by molecular alterations (mutations, deletions, gene fusions) involving genes and proteins impinging upon different cellular pathways.The transition from PTC/FTC to poorly differentiated (PDTCs) and ATCs is attributed to additional molecular alterations.Medullary thyroid carcinoma (MTC) originates from para-follicular C-cells and is prevalently characterized by RET or RAS mutations. > In order to better classify the molecular alterations detected in thyroid cancer, we will initially discuss RTK-related upstream signaling pathways involved in tumorigenesis and subsequently focus on the effectors of these pathways.Finally, we will describe alterations contributing to thyroid carcinogenesis that involve pivotal cellular functions.In order to better classify the molecular alterations detected in thyroid cancer, we will initially discuss RTK-related upstream signaling pathways involved in tumorigenesis and subsequently focus on the effectors of these pathways.Finally, we will describe alterations contributing to thyroid carcinogenesis that involve pivotal cellular functions.

[11] Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway

Authors: Hao Zhang, Ning Hu
Year: 2018
Venue: Molecular Medicine Reports
URL: https://www.semanticscholar.org/paper/d55f3824298aceb87e57be03aa068b50d4eb8c54
DOI: 10.3892/mmr.2018.9119
PMID: 29901196
PMCID: 6072153
Citations: 12
Influential citations: 1
Summary: TERT could induce thyroid carcinoma cell proliferation mainly through the PTEN/AKT signaling pathway according to the molecular mechanisms.
Evidence snippets:
Snippet 1 (score: 0.476) > Thyroid carcinoma is the most common endocrine malignant tumor in the world, which accounts for 94.5% of all endocrine tumors. The incidence of thyroid cancer has been increasing since the end of last century and has ranked the top of the list of head and neck cancers (1,2). Papillary thyroid cancer (PTC) is the most common pathology type in thyroid cancer, ~90% of thyroid carcinoma. 85-90% incidence of thyroid cancer was caused by PTC. More women are involved in it than men, and most of them are accompanied by cervical lymph node metastasis. PTC is a low-grade malignancy, the main clinical symptoms of which are the slow growth of thyroid mass and multifocal occurrence, tendency of regional lymph nodes metastasis. The prognosis of PTC is good after proper effective treatment, with 5-year survival rate of 95%, and 10-year survival rate of above 90% (3). However, some PTC is of high invasion ability, and some of them has the tendency of dedifferentiation to form low-differentiated or non-differentiated cancers and result in the decreasing of survival rate and life quality (4). > The occurrence and development of thyroid cancer is a complicated process including a variety of oncogenes, signaling pathway and aberrant proteins, resulting in abnormal proliferation and mutation. Therefore, study on PTC molecular mechanism will help looking for new biomarkers for PTC early diagnosis, lymph nodes metastasis prediction, treatment and prognosis. > Telomerase is a self-templated reverse transcriptase, containing two subunits of TERC (telomerase RNA component) and TERT (telomerase reverse transcriptase). As the Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway core subunit of telomerase, TERT catalyzes TERC reverse transcription to regulate telomerase activity and maintain telomere length (5)(6)(7). Over-expression of TERT could promote the proliferation of mesenchymal stem cells, epithelial cells and nerve cells (8,9).

[12] Growth‐associated protein 43 promotes thyroid cancer cell lines progression via epithelial‐mesenchymal transition

Authors: C. Zheng, Rui-da Quan, Chen-Yong Wu, Jing Hu, Bangyi Lin et al.
Year: 2019
Venue: Journal of Cellular and Molecular Medicine
URL: https://www.semanticscholar.org/paper/d73055efdaacac199d65ba868c199f4732ca21cc
DOI: 10.1111/jcmm.14460
PMID: 31568662
PMCID: 6850924
Citations: 15
Summary: GAP43 is a gene which was associated with PTC and might be a potential therapeutic target and it is indicated that GAP43 could modulate the expression of epithelial‐mesenchymal transition‐related proteins, which could influence invasion and migration.
Evidence snippets:
Snippet 1 (score: 0.474) > Thyroid cancer (TC) is maintaining at a high incidence level and it becomes one of the most common cancers in worldwide. 1,2 The US National Cancer Institute anticipated 53 990 new cases besides 2110 death numbers of patients because of TC in the USA in 2018. 3,4 sides, the papillary thyroid cancer (PTC) is the commonest subtype of TC (accounts for 80%-90%). 5 Although the incidence of PTC is high, it is generally considered that PTC is relatively curable and has a good prognosis. 6,7 After a surgical operation or radio-iodinated therapy, patients with PTC show satisfactory prognosis besides a general 10-year survival rate of 90%. 7 However, clinical course of PTC usually follows indolent and carries excellent prognosis, it is still highly metastatic and relapses after routine treatment. 5 ][10] LNM has been shown to occur in approximately 20% of all PTC patients, and regional recurrence occurred in 10% of patients undergoing total thyroidectomy. 11 So, it is vital for us to facilitate the in-depth investigation of the mechanism of PTC and help doctors to provide an appropriate treatment approach. > The incidence and development of PTC are primarily affected by genomic alternation, involving stimulation of oncogene and silencing of a tumour suppressor gene. Accumulating reports have been published about molecular mechanisms of PTC over nearly a period of 20 years. B-type Raf kinase (BRAF) V600E, a famous gene mutation, promotes PTC tumorigenesis and progression by abnormally stimulating the mitogen-activated pathway kinase pathway. 12 Besides, some notable mutations such as RAS mutation, 13 TERT mutation, 14 PTEN mutation, 15 PIK3CA mutation 16,17 and TP53 mutation 18 also show a significant part in thyroid carcinoma. Numerous researchers have made remarkable progress in TC gene research, but many characters of PTC are yet relatively unspecified. Hence, examining for new potential markers and clarifying molecular mechanisms in the improvement of thyroid carcinoma is still essential. > In our previous study, we have conducted next-generation of 19 pairs of PTC tissues and adjacent normal thyroid tissue. 19

[13] High Genetic Diversity and No Evidence of Clonal Relation in Synchronous Thyroid Carcinomas Associated with Hashimoto’s Thyroiditis: A Next-Generation Sequencing Analysis

Authors: C. Molnár, E. Bádon, A. Mokánszki, A. Mónus, L. Beke et al.
Year: 2020
Venue: Diagnostics
URL: https://www.semanticscholar.org/paper/935eb885fe76e6735a9baf1789f52742ec570f53
DOI: 10.3390/diagnostics10010048
PMID: 31963551
PMCID: 7167801
Citations: 9
Summary: The different BRAF statuses in coincident thyroid carcinoma foci within the same organ outline a special challenge for molecular follow-up and therapeutic decision-making.
Evidence snippets:
Snippet 1 (score: 0.471) > Thyroid carcinoma is the most frequent endocrine neoplasia, the incidence of which is increasing worldwide [1,2]. Major etiological factors include environmental and direct thyrotoxic effects, and selected comorbidities such as autoimmune thyroid disease are also considered as associated factors [3,4]. While the immunological background and pathological consequences of autoimmune lymphocytic thyroiditis and, more recently, IgG4-related chronic inflammation have been gradually elucidated, the exact mechanisms of subsequent carcinogenesis are mostly unknown. Hashimoto's thyroiditis (HT) is one of the most frequent autoimmune thyroid disorders characterized by massive lymphocytic infiltrate and progressive destruction of the thyroid parenchyma [5,6]. The autoimmune attack results in direct cellular toxicity, and regeneration is associated with endocrine and metabolic/oxidative stress at the level of the thyroid follicular epithelium [7,8]. Parenchymal hypofunction, on the other hand, triggers a constant proliferative stimulus by thyroid-stimulating hormone (TSH), enabling increased survival and adaptive selection, which are both important factors in the process of carcinogenesis. According to the current view, not only has the association between HT and especially papillary-type thyroid carcinoma (PTC) been established, but the frequent multifocality of PTC can also be explained by HT-related injury and consequent stimulatory mechanisms [6,9]. > With the recent developments of genomic DNA testing, a sharpened picture of relevant gene alterations and molecular pathways can also be provided for thyroid malignancies. The availability of next-generation sequencing (NGS) approaches enables the large-scale analysis of cancer genotype from archived pathological material [10,11]. Several well-documented studies using NGS were performed to define the mutational spectrum of thyroid carcinoma, especially focusing on advanced and anaplastic carcinoma cohorts [12,13]. Data obtained by extended cancer-related gene panel analysis delineated MAPK and PI3K pathway mutations as contributing to aggressive behavior.

[14] Genome-wide expression analysis suggests a crucial role of dysregulation of matrix metalloproteinases pathway in undifferentiated thyroid carcinoma

Authors: J. Espinal-Enríquez, S. Muñoz-Montero, Ivan Imaz-Rosshandler, Aldo Huerta-Verde, Carmen Mejía et al.
Year: 2015
Venue: BMC Genomics
URL: https://www.semanticscholar.org/paper/aaf44d01ab95964e2cee2acee8339ddf6bd039c7
DOI: 10.1186/s12864-015-1372-0
Summary: The genome-wide analysis of thyroid carcinoma subtypes emphasizes the preponderance of pathway-dysregulation mechanisms over simple gene-malfunction as the main mechanism involved in the development of a cancer phenotype.
Evidence snippets:
Snippet 1 (score: 0.471) > Thyroid cancer (TC) is the most common malignant cancer of the Endocrine System. Histologically, there are three main subtypes of TC: follicular, papillary and anaplastic. Diagnosing a thyroid tumor subtype with a high level of accuracy and confidence is still a difficult task because genetic, molecular and cellular mechanisms underlying the transition from differentiated to undifferentiated thyroid tumors are not well understood. A genome-wide analysis of these three subtypes of thyroid carcinoma was carried out in order to identify significant differences in expression levels as well as enriched pathways for non-shared molecular and cellular features between subtypes. Inhibition of matrix metalloproteinases pathway is a major event involved in thyroid cancer progression and its dysregulation may result crucial for invasiveness, migration and metastasis. This pathway is drastically altered in ATC while in FTC and PTC, the most important pathways are related to DNA-repair activation or cell to cell signaling events. A progression from FTC to PTC and then to ATC was detected and validated on two independent datasets. Moreover, PTX3, COLEC12 and PDGFRA genes were found as possible candidates for biomarkers of ATC while GPR110 could be tested to distinguish PTC over other tumor subtypes. The genome-wide analysis emphasizes the preponderance of pathway-dysregulation mechanisms over simple gene-malfunction as the main mechanism involved in the development of a cancer phenotype.

[15] Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

Authors: W. Tulalamba, T. Janvilisri
Year: 2012
Venue: International Journal of Cell Biology
URL: https://www.semanticscholar.org/paper/307cb9186444d9dad6e2e3b53763be0de76de186
DOI: 10.1155/2012/594681
PMID: 22500174
PMCID: 3303613
Citations: 93
Influential citations: 5
Summary: The molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression and the important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.
Evidence snippets:
Snippet 1 (score: 0.470) > In the pregenomic eras, highly integrated and complex circuitry of molecular signaling in NPC pathogenesis was only partially understood. Over the past decade, the knowledge of the molecular mechanisms in NPC carcinogenesis has been rapidly accumulated. Dysregulation and abnormal protein expression of molecules in certain signaling pathways involved in cellular functions including proliferation, adhesion, survival, and apoptosis has been demonstrated in the NPC cells. Detailed information on the complex network in signaling pathway leading to a coordinated pattern of gene expression and regulation in NPC will undoubtedly provide important clues to develop novel prognostic and therapeutic strategies for this cancer. Refining molecular markers into clinically relevant assays may assist in the detection of NPC in asymptomatic patients, as well as stage classification and monitoring disease progression and treatments. Furthermore, selective regulation of particular proteins targeting cancer cell proliferation, invasion, and apoptosis is a hopeful prospect for future anticancer therapy that slow disease progression and improve survival.

[16] Bioinformatics analysis to screen key genes in papillary thyroid carcinoma

Authors: Yuanhu Liu, Shuwei Gao, Yaqiong Jin, Yeran Yang, J. Tai et al.
Year: 2019
Venue: Oncology Letters
URL: https://www.semanticscholar.org/paper/b24ecef22e13d5187ed1c036d514bbd3f2af07ec
DOI: 10.3892/ol.2019.11100
PMID: 31897130
PMCID: 6924100
Citations: 15
Summary: The findings of the present study suggest that these genes and related pathways are involved in key events of PTC progression and facilitate the identification of prognostic biomarkers.
Evidence snippets:
Snippet 1 (score: 0.462) > Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, and its incidence has been on the increase in recent years. However, the molecular mechanism of PTC is unclear and misdiagnosis remains a major issue. Therefore, the present study aimed to investigate this mechanism, and to identify key prognostic biomarkers. Integrated analysis was used to explore differentially expressed genes (DEGs) between PTC and healthy thyroid tissue. To investigate the functions and pathways associated with DEGs, Gene Ontology, pathway and protein-protein interaction (PPI) network analyses were performed. The predictive accuracy of DEGs was evaluated using the receiver operating characteristic (ROC) curve. Based on the four microarray datasets obtained from the Gene Expression Omnibus database, namely GSE33630, GSE27155, GSE3467 and GSE3678, a total of 153 DEGs were identified, including 66 upregulated and 87 downregulated DEGs in PTC compared with controls. These DEGs were significantly enriched in cancer-related pathways and the phosphoinositide 3-kinase-AKT signaling pathway. PPI network analysis screened out key genes, including acetyl-CoA carboxylase beta, cyclin D1, BCL2, and serpin peptidase inhibitor clade A member 1, which may serve important roles in PTC pathogenesis. ROC analysis revealed that these DEGs had excellent predictive performance, thus verifying their potential for clinical diagnosis. Taken together, the findings of the present study suggest that these genes and related pathways are involved in key events of PTC progression and facilitate the identification of prognostic biomarkers.

[17] The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer

Authors: Sai-Li Duan, Min Wu, Zhe-Jia Zhang, Shi Chang
Year: 2023
Venue: Journal of Translational Medicine
URL: https://www.semanticscholar.org/paper/848fc3da01105356f5b19f4b99e3b42e0d89f78d
DOI: 10.1186/s12967-023-04617-2
PMID: 37853445
PMCID: 10585934
Citations: 20
Influential citations: 1
Summary: Past and recent advances in the understanding of the reprogramming of glucose metabolism in thyroid cancer cells are summarized, which are expected to yield new therapeutic approaches for patients with special pathological types of thyroid cancer by targeting reprogrammed glucose metabolism.
Evidence snippets:
Snippet 1 (score: 0.461) > Thyroid cancer (TC) is an endocrine system tumor originating from follicular thyroid cells and parafollicular C cells, and its incidence rate is rising worldwide [1,2].Most thyroid malignancies (> 95%) are differentiated thyroid cancers (DTCs), which include papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) [3].Lymph node metastasis is a common clinical feature of DTC, and a considerable portion of DTC is prone to early cervical lymph node metastases (approximately 20-70%), which is an important factor affecting the prognosis of DTC patients [4,5].Despite the widespread use of multimodality treatment (ie, surgery, chemotherapy, and radiotherapy), survival rates have not improved much over the past few decades, suggesting that new treatment options should be explored [6][7][8].Therefore, we recommend seeking other effective treatments for TC.Probing the molecular mechanism of disease progress, and developing new targeted drugs remain the focus of TC research [9].Initiation and progression of TC involves multiple genetic and epigenetic alterations, among which common mutations found in TC are point mutations in the BRAF and RAS genes as well as RET/PTC and PAX8/ PPARγ chromosomal rearrangements [10,11].These alterations often lead to anomalies in the proliferation, Page 2 of 20 Duan et al. Journal of Translational Medicine (2023) 21:735 differentiation and metabolism patterns of thyroid follicular cells, acting synergistically to amplify their effects on thyroid tumor development.These mutations are crucial for the abnormal activation of the MAPK and PI3K-AKT signaling pathways, which primarily regulate cell proliferation and differentiation, but also directly regulate the activity of oxidative phosphorylation, cellular glucose uptake and aerobic glycolytic processes [12,13].Cancer cells frequently undergo a reorganization of metabolism to promote growth, survival, proliferation and long-term maintenance [14].

[18] A Comprehensive Risk Assessment and Stratification Model of Papillary Thyroid Carcinoma Based on the Autophagy-Related LncRNAs

Authors: Yongrun Mu, Fu-Jiang Song, Kai Yuan, Zili Zhang, Yan Lu et al.
Year: 2022
Venue: Frontiers in Oncology
URL: https://www.semanticscholar.org/paper/900b75f99d7ac2d2af53131fe7b7f31d883fbd5a
DOI: 10.3389/fonc.2021.771556
PMID: 35284335
PMCID: 8908373
Citations: 3
Summary: A novel risk stratification for PTC based on the expression profiles of autophagy-related lncRNAs is established and knockdown of the CRNDE in PTC increased the sensitivity to sorafenib.
Evidence snippets:
Snippet 1 (score: 0.460) > Thyroid carcinoma is the most common endocrine malignant tumor, and 90% of this tumor type is made up of papillary carcinoma histologically (1). The improvement of thyroidbased diagnostic procedures, such as radiographic imaging and fine-needle aspiration, has contributed directly to the rapid increase of new discovered cases (2). Similarly, papillary carcinoma accounts for most of the increase (3). However, the other histological subtypes (anaplastic, medullary, and follicular) do not change markedly (4,5). The sharp increase in mortality due to PTC has garnered increased concern from the public (3,6,7). > With the research on papillary carcinoma mainly focused on genetics, transcriptomics proteomics, and epigenetics, mechanistic knowledge is growing rapidly. Therefore, determining the correlation of the clinicopathological information with the genomic alternations and transcriptome has become a new area of research for many researchers (8). > The increasing risk of small thyroid nodes due to overdiagnosis alone remains controversial among clinical decision makers. Although the eighth edition of the A m e r i c a n J o i n t C o m m i t t e e o n C a n c e r -U n i o n fo r International Cancer Control (AJCC-UICC) staging system describes that most patients at low risk have a lower mortality for differentiated thyroid cancer, there is a crucial discussion about initial therapeutic decision-making and the clinical management of those newly diagnosed (9), especially regarding the requirement for active surveillance or thyroid surgery (1). > Autophagy is a type II programmed cell death process, which directly controls physiological mechanisms by degradation of proteins and organelles to achieve homeostasis (10). It is an important pathway necessary to adjust to various stresses (11). Nevertheless, dysregulation of autophagy involved in multiple diseases, including cancer (12)(13)(14), results in both tumor suppression and oncogenesis at different stages of cancer development.

[19] Let-7a inhibits migration, invasion and tumor growth by targeting AKT2 in papillary thyroid carcinoma

Authors: Bin Zhou, Hailin Shan, Ying Su, Kai Xia, Runlong Zou et al.
Year: 2017
Venue: Oncotarget
URL: https://www.semanticscholar.org/paper/333d40c672cc41bc465694b23902c219bb61f761
DOI: 10.18632/oncotarget.19261
PMID: 29050238
PMCID: 5642513
Citations: 27
Influential citations: 1
Summary: Findings suggest that let-7a acts as a novel suppressor by targeting the AKT2 gene and might be a candidate target for the development of novel therapeutic strategies to treat papillary thyroid carcinoma.
Evidence snippets:
Snippet 1 (score: 0.458) > Thyroid carcinoma is the most common endocrine malignancy of the thyroid in adults [1]. Papillary thyroid carcinoma (PTC), the most prevalent histology subtype (80% of cases), and its incidence have been increased a lot over the past few decades [2,3]. Multifocal lesions are one of clinical characteristics of PTC and provide a power evidence of lymph node invasion and distant metastasis [4,5]. Currently, the invasion and metastasis of PTC are the major cause of fatal outcome and, therefore, it is essential to elucidate the molecular mechanisms of PTC progression to facilitate the development of novel targeted therapies. > MicroRNAs (miRNAs) are non-protein-coding, 19-22 nucleotide RNAs that regulate gene expression posttranscriptionally by targeting their mRNAs, leading to mRNA degradation or inhibition of protein translation [6,7]. MiRNAs include miR-187, -221, -31, -146b are known to play important roles in PTC. In particular, studies showed that expression levels of let-7a are downregulated in many types of cancers, including PTC [8][9][10], but whether its levels are correlated with PTC clinical stages is not known yet. In addition, the roles and mechanisms of let-7a in regulating cell proliferation, migration, invasion and tumorigenesis far from being fully elucidated. > AKT2 (v-AKT murine thymoma viral oncogene homologue 2), a key downstream effector of the phosphatidylinositol 3-kinase(PI3K) pathway [11]. Many studies show that AKT2 is involved in cancer development and play a great role in cell cycle, apoptosis, proliferation and migration [12,13]. Recent studies indicate that AKT2 could be regulated by microRNAs. MiR-137 targeted AKT2 to suppresses tumor growth and metastasis in human hepatocellular carcinoma [14]. MiR-302b inhibited cell cycle in human hepatocellular carcinoma by targeting AKT2 [15].

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Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Papillary Thyroid Carcinoma. Core disease mechanisms, molecular and cellul...

Relevant Papers

[1] Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer

[2] Redox metabolism correlates with cellular turnover and clinical phenotype of papillary thyroid carcinoma and colloid goiter

[3] Network medicine approaches for identification of novel prognostic systems biomarkers and drug candidates for papillary thyroid carcinoma

[4] In silico Analysis of Publicly Available Transcriptomics Data Identifies Putative Prognostic and Therapeutic Molecular Targets for Papillary Thyroid Carcinoma

[5] Systems biology approach delineates critical pathways associated with papillary thyroid cancer: a multi-omics data analysis

[6] Association of CYP2D6*4 gene polymorphism with early papillary thyroid carcinoma

[7] Identification of Hub Genes in Anaplastic Thyroid Carcinoma: Evidence From Bioinformatics Analysis

[8] Identification of Differentially Expressed Kinase and Screening Potential Anticancer Drugs in Papillary Thyroid Carcinoma

[9] Identification of genes associated with lymph node metastasis in papillary thyroid carcinoma by weighted gene co-expression network analysis

[10] Molecular Alterations in Thyroid Cancer: From Bench to Clinical Practice

[11] Telomerase reverse transcriptase induced thyroid carcinoma cell proliferation through PTEN/AKT signaling pathway

[12] Growth‐associated protein 43 promotes thyroid cancer cell lines progression via epithelial‐mesenchymal transition

[13] High Genetic Diversity and No Evidence of Clonal Relation in Synchronous Thyroid Carcinomas Associated with Hashimoto’s Thyroiditis: A Next-Generation Sequencing Analysis

[14] Genome-wide expression analysis suggests a crucial role of dysregulation of matrix metalloproteinases pathway in undifferentiated thyroid carcinoma

[15] Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

[16] Bioinformatics analysis to screen key genes in papillary thyroid carcinoma

[17] The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer

[18] A Comprehensive Risk Assessment and Stratification Model of Papillary Thyroid Carcinoma Based on the Autophagy-Related LncRNAs

[19] Let-7a inhibits migration, invasion and tumor growth by targeting AKT2 in papillary thyroid carcinoma

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