Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access
Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc
Journal website http://www.gastrores.org

Review

Volume 12, Number 6, December 2019, pages 275-282


Molecular Classification of Gastric Adenocarcinoma

Tables

Table 1. Intrinsic Subtypes
 
G-INT GCG-DIF GC
G-INT: genomic intestinal; G-DIF: genomic diffuse; GC: gastric cancer; AURKB: aurora kinase B; CDH17: cadherin 17; ELOVL5: ELOVL family member 5; FUT2: fucosyltransferase 2; LGALS4: lectin; 5-FU: 5-fluorouracil.
HistologyIntestinal histology (91/133)Diffuse histology (64/107)
Molecular alterationsGenes up-regulated were related to carbohydrate and protein metabolism (FUT2) and cell adhesion (LGALS4, CDH17)Cell proliferation (AURKB) and fatty acid metabolism (ELOVL5) functional annotations were enriched
Treatment reactionIn vitro study, G-INT cell lines were sensitive to 5-FU and oxaliplatinIn vitro study, G-DIF cell lines were more sensitive to cisplatin
Patients with G-INT tumors may derive benefit from adjuvant 5-FU-based therapy
PrognosisSuperior overall survivalPoor

 

Table 2. Lei Subtypes
 
Proliferative GCMetabolic GCMesenchymal GC
GC: gastric cancer; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: gene ontology; PI3K/Akt/mTOR: phosphatidylinositol 3-kinase-AKT-mTOR; DNA: deoxyribonucleic acid.
HistologyIntestinal (73.6%)Intestinal (53.6%)Diffuse (58.2%)
Molecular alterationsCharacterized by gene sets related to the cell cycle: KEGG cell cycle, KEGG DNA replication, and 13 GO gene setsCharacterized by gene sets from several KEGG metabolism pathways and GO digestionOver-represents the following gene sets: KEGG focal adhesion, KEGG extracellular-matrix–receptor interaction, and GO cell adhesion
High number of TP53 mutationsLow TP53 mutationsLow TP53 mutations
Druggable targetsThe PI3K-AKT-mTOR pathway could be an effective drug target
Treatment reactionMore sensitive to 5-fluorouracil treatmentThe cell lines of this subtype were particularly sensitive to compounds targeting the PI3K/AKT/mTOR inhibitors in vitro study
PrognosisShorter disease-free survival

 

Table 3. TCGA Subtypes
 
SubtypesEBV-positiveMSIGSCIN
ARID1A: AT-rich interactive domain-containing protein 1A; BCOR: B-cell lymphoma 6 corepressor; CIN: chromosomal instability; GS: genomically stable; GC: gastric cancer; CIMP: CpG island methylator phenotype; DNMT3b: DNA methyltransferase 3b; EBV: Epstein-Barr virus; EGFR: epithelial growth factor receptor; ERBB2: Erb-B2 receptor tyrosine kinase 2; JAK2: Janus-associated kinase 2; LMP2A: latent membrane protein 2A; LELC: lymphoepithelioma-like carcinoma; MSI: microsatellite instability; PI3K: phosphatidylinositol-3-kinase; RHOA: Ras homolog family member A; TCGA: The Cancer Genome Atlas; PD-L1/2: programmed death ligand-1/2; CDK6: cell division protein kinase 6.
Frequency8.8%21.7%19.7%49.8%
DemographicMale patients (81%)Old age (median 72 years)Young age (median 59 years)No special
HistologyDiffuse histologyIntestinal histology
Main locationFundus or body (62%)Gastro-esophageal junction/cardia (65%)
Molecular alterationsEBV-CpG island methylator phenotype (CIMP)Gastric-CIMPCDH1, RHOA mutationTP53 mutation
PD-L1/2, JAK2 overexpressionHypermutation in TP53, PIK3CA, ERBB3, ARID1ACLDN18-ARHGAP fusionRTK-RAS activation
Mutation in PIK3CA, ARID1A, BCORMLH1 silencingCell adhesion, angiogenesis pathways enrichedMutations of SMAD4 and APC
CDKN2A silencingMitotic pathways activationRare TP53 mutations
Immune cell signalingCommune changes in the genes of CMHI
Rare TP53 mutations
Potential targetsPIK3CA, JAK2, PD-L1/PD-L2PIK3CA, ERBB2/3, EGFR, PD-L1, MLH1 silencingRHOA, CLDN18RTKs, EGFR, VEGFA, CCNE1, CCND1, CDK6
Treatment reactionNo respond to adjuvant chemotherapy

 

Table 4. ACRG Subtypes
 
SubtypesMSI GCMSS/EMT GCMSS/TP53- GCMSS/TP53+ GC
ACRG: Asian Cancer Research Group; ARID1A: AT-rich interactive domain-containing protein 1A; CDH1: E-cadherin; GC: gastric cancer; MSS/EMT: microsatellite stable/epithelial-mesenchymal transition; MSS/TP53+: microsatellite stable/epithelial/TP53 intact; MSS/TP53-: microsatellite stable/epithelial/TP53 loss; MSI: microsatellite instability; PI3K: phosphatidylinositol-3-kinase; RHOA: Ras homolog family member A; PD-L1: programmed death ligand-1.
Frequency22.7%15.3%35.7%26.3%
DemographicDiagnosed at a significantly younger ageMaleMale
HistologyIntestinal histology (> 60%)Diffuse histology (> 80%)Intestinal histologyIntestinal histology
Molecular alterationsSilencing of MLH1 geneLoss of CDH1Highest prevalence of TP53 and RHOA mutationsFrequent EBV infection
Mutations in ARID1A, MTOR, KRAS, PIK3CA, ALK, PTENLoss of cellular adhesion, angiogenesis, motilityAPC, ARID1A, KRAS, PIK3CA, SMAD4 enrichedFrequent mutations in ARID1A, PIK3CA, SMAD4, APC
Overexpression of PD-L1
T cell infiltrate
PrognosisBest overall prognosis, lowest recurrence rate (22%)Worst prognosis, highest recurrence rateIntermediateIntermediate