| Domain | Core facts | Suggested ontology terms | Key evidence |
|---|---|---|---|
| Identity / identifiers | Gastric adenocarcinoma is the dominant histologic form of stomach cancer; ~90% of gastric cancers are adenocarcinomas. MONDO:0005036. Disease-level knowledge here is derived mainly from aggregated literature/guidelines, not individual EHRs. | MONDO:0005036; MeSH: Stomach Neoplasms / Adenocarcinoma; ICD-11 gastric carcinoma terms | (pqac-00000005, pqac-00000027) |
| Histology / classification | Lauren types: intestinal, diffuse, mixed. Early gastric cancer is limited to mucosa/submucosa; advanced disease invades muscularis propria or deeper. WHO/Lauren classification remains standard pathology framework. | NCIT gastric adenocarcinoma; HPO: gastric adenocarcinoma; UBERON: stomach | (pqac-00000001, pqac-00000029) |
| Molecular classes | TCGA framework: EBV-positive, MSI, genomically stable (GS), chromosomal instability (CIN). EBV/MSI enrich for immune sensitivity; GS often overlaps diffuse-type biology; CIN often associates with RTK amplifications. | NCIT: Epstein-Barr virus positive tumor; MSI-high; chromosomal instability | (pqac-00000003, pqac-00000004) |
| Major etiologies / risks | Major causes/risk factors: Helicobacter pylori, smoking, high-salt/processed meat diets, low fruit/vegetable intake, atrophic gastritis, autoimmune gastritis; obesity/GERD more relevant for proximal/GEJ disease; EBV contributes in a subset. | CHEBI: sodium chloride; NCBITaxon: Helicobacter pylori; HPO: chronic gastritis, intestinal metaplasia | (pqac-00000005, pqac-00000013) |
| Protective / preventive factors | H. pylori eradication lowers gastric cancer incidence; benefit is greatest before advanced precancerous lesions but may still extend later in life. Population “screen-and-treat” is the leading prevention strategy in many regions. | NCIT: Helicobacter pylori eradication therapy; preventive screening | (pqac-00000012, pqac-00000016) |
| Germline genes | Hereditary diffuse gastric cancer is chiefly due to CDH1 and less often CTNNA1; autosomal dominant. CDH1 loss usually needs a second hit, commonly promoter hypermethylation. APC underlies GAPPS, a distinct hereditary gastric neoplasia syndrome. | HGNC: CDH1, CTNNA1, APC; MONDO hereditary diffuse gastric adenocarcinoma | (pqac-00000018, pqac-00000019, pqac-00000020, pqac-00000000) |
| Major somatic drivers | Recurrently implicated genes/pathways include TP53, ARID1A, KRAS, RHOA, PIK3CA, RNF43, KMT2D, SMAD4, ERBB2 and angiogenic signaling via KDR/VEGFR2. HER2 amplification is a key actionable alteration; RHOA is enriched in diffuse/GS disease. | HGNC: TP53, ARID1A, KRAS, RHOA, PIK3CA, ERBB2, RNF43, KMT2D, SMAD4, KDR | (pqac-00000000, pqac-00000003, pqac-00000004) |
| Mechanisms / pathways | Carcinogenesis reflects interaction of microbial inflammation, epithelial injury, stem/progenitor DNA damage, Wnt/MAPK/PI3K signaling, EMT/invasion, and immune evasion. In HDGC, E-cadherin loss disrupts adhesion and spindle orientation; in experimental systems H. pylori plus Apc loss augments DNA damage in gastric stem/progenitor cells. | GO: cell adhesion, Wnt signaling, MAPK cascade, PI3K-AKT signaling, epithelial to mesenchymal transition; CL: gastric epithelial cell, macrophage, CD8-positive T cell | (pqac-00000018, pqac-00000019, pqac-00000008) |
| Clinical phenotypes | Common manifestations include dyspepsia, weight loss, early satiety, abdominal pain, iron-deficiency anemia, bleeding, obstruction, and metastatic symptoms. Diffuse/signet-ring cancers may infiltrate the wall with less obvious gland formation. | HPO: Abdominal pain, Early satiety, Weight loss, Iron deficiency anemia, Gastrointestinal hemorrhage, Gastric outlet obstruction | (pqac-00000001, pqac-00000005, pqac-00000027) |
| Anatomy affected | Primary organ: stomach, especially mucosa/glandular epithelium; proximal/GEJ and distal/antral patterns differ epidemiologically. Common secondary sites include lymph nodes, peritoneum, liver, lung, and ovary/adnexa; peritoneal spread is a major complication. | UBERON: stomach, gastric mucosa, lymph node, liver, peritoneum, lung; CL: gastric epithelial cell | (pqac-00000005, pqac-00000027) |
| Diagnostics / biomarkers | Diagnostic gold standard: upper endoscopy with biopsy reviewed by experienced pathology; multiple biopsies improve accuracy. Staging uses CT chest/abdomen/pelvis; EUS refines depth/nodes; laparoscopy with peritoneal lavage detects occult peritoneal disease. Core biomarkers: HER2, MMR/MSI, PD-L1 CPS, CLDN18.2; NGS and liquid biopsy are emerging/investigational in guidelines. | NCIT: Endoscopy, Biopsy, Endoscopic ultrasonography, Computed tomography, Diagnostic laparoscopy; HGNC/biomarkers: ERBB2, PD-L1(CD274), CLDN18, MMR genes | (pqac-00000026, pqac-00000027, pqac-00000031) |
| Treatment by stage / biomarker | Very early disease: EMR/ESD in selected superficial lesions. Resectable locally advanced disease: gastrectomy plus perioperative chemotherapy (FLOT in many Western settings) or adjuvant strategies in East Asia. Metastatic disease: fluoropyrimidine-platinum backbone, adding trastuzumab for HER2+, pembrolizumab/nivolumab-based therapy by PD-L1 or MSI status, and zolbetuximab for CLDN18.2+ HER2-negative disease; anti-VEGFR2 strategies are standard in later lines in many regions. | NCIT: Gastrectomy, Endoscopic mucosal resection, Endoscopic submucosal dissection, FLOT regimen, Trastuzumab, Pembrolizumab, Nivolumab, Zolbetuximab, Ramucirumab | (pqac-00000004, pqac-00000026, pqac-00000027) |
| Prevention / screening | East Asian programs support endoscopic screening; Korea screens adults ≥40 every 2 years and Japan uses endoscopy from age 50. China’s county-level endoscopic program was associated with a 15% mortality decrease. In Europe, organized population H. pylori screen-and-treat is the main currently supportable strategy, while direct endoscopic screening evidence remains less mature. | NCIT: Mass screening, Endoscopy, Helicobacter pylori test-and-treat | (pqac-00000011, pqac-00000012, pqac-00000014, pqac-00000015) |
| Prognosis | Prognosis depends strongly on stage, TNM class, age, surgery, and treatment response. Advanced/metastatic gastric cancer still has poor median survival, often <12 months with conventional chemotherapy alone, though biomarker-guided immunotherapy/targeted therapy has improved outcomes. In high-risk Chinese older cohorts, 3-year OS declined from 58.5% to 34.4% across 2010-2019, underscoring ongoing mortality burden. | HPO: reduced survival; NCIT: overall survival, progression-free survival | (pqac-00000002, pqac-00000004) |
| Epidemiology | Gastric cancer burden is geographically concentrated in East Asia and is higher in males and older adults. In Asia (GLOBOCAN 2020), ASIR was 14.3/100,000 overall, 20.4 in males and 8.7 in females; ASMR was 10.0 overall. | NCIT: incidence, mortality; demographic descriptors | (pqac-00000011, pqac-00000012) |
| Model systems | Key translational models include patient-derived organoids, gastric organoid infection systems, PDX models, and genetically engineered mouse/organoid HDGC models. Single-cell/spatial studies profile epithelial, fibroblast, macrophage, B-cell, neutrophil, and CD8 T-cell states; experimentally supported axes include IL1B-IL1R2, CXCL5-CXCR2, and CCL28-CCR10. Main limitations: partial loss of native microenvironment, biomarker heterogeneity, and incomplete capture of long-term evolution. | NCIT: Patient-derived xenograft model, Organoid, Single-cell RNA sequencing, Spatial transcriptomics; CL: macrophage, fibroblast, B cell, neutrophil, CD8-positive T cell | (pqac-00000006, pqac-00000007, pqac-00000008) |


*Table: This compact table summarizes the core disease-knowledge domains for gastric adenocarcinoma, including classification, etiology, genetics, clinical features, diagnostics, treatment, prevention, prognosis, and models. It is designed as a concise scaffold for populating a disease knowledge base with ontology suggestions and evidence anchors.*