Research progress on molecular classification of gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Songtao , GUO Weihan , SHI Anni , ZHU Zhengyu ,  WANG Guihua

Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science & Technology, Wuhan 430030, P. R. China;

Corresponding?author：

WANG Guihua, Email: ghwang@tjh.tjmu.edu.cn

Keywords：

gastric cancer; molecular classification; precision medicine; tumor microenvironment; multi-omics

DOI：

10.7507/1007-9424.202604097

Video：

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Objective To understand the research advances in molecular classification systems of gastric cancer and explore their clinical application value in precision diagnosis and treatment, as well as future development directions. Method A literature search was conducted to identify and summarize the classic classification systems, including the Singapore-Duke typing, The Cancer Genome Atlas (TCGA) typing, and the Asian Cancer Research Group (ACRG) typing, as well as novel precision typing frameworks driven by cutting-edge technologies such as single-cell sequencing, spatial transcriptomics, epigenetics, metabolomics, and multi-omics integrative analysis. Results Gastric cancer is characterized by high heterogeneity, and traditional pathological typing is difficult to meet the requirements of precision diagnosis and treatment. Among the classic molecular classifications, the Singapore-Duke classification classifies gastric cancer into proliferative, mesenchymal, and metabolic subtypes, and which are correlated with drug sensitivity. According to the multi-omics features, the TCGA classification categorizes gastric cancer into four subtypes: Epstein-Barr virus (EBV)-positive, microsatellite instability (MSI), genomically stability (GS), and chromosomal instabilty (CIN), among which EBV-positive and MSI subtypes are associated with the best prognosis, while the GS subtype shows the worst prognosis. The ACRG classification (Asian cohort) categorizes gastric cancer into MSI, microsatellite stable (MSS)/TP53-active, MSS/TP53-inactive, and MSS/epithelial-mesenchymal transition (EMT) subtypes, among which MSI tumors show the best prognosis, and MSS/EMT tumors the worst. Regarding novel frontier classifications, tumor microenvironment ecotypes and cancer-associated fibroblast subpopulations are identified by single-cell and spatial transcriptomics. Additionally, immune consensus subtypes, a PANoptosis-related long non-coding RNA prognostic model, and tumor immune microenvironment classifications, and other subtypes have been constructed through epigenetics, metabolomics, and multi-omics integrative analysis. In clinical translation, different molecular subtypes are matched with corresponding therapeutic strategies, and the combination of molecular classification and TNM staging is enabled to improve the accuracy of prognostic evaluation. Conclusions Molecular classification of gastric cancer provides a stratification basis for precise diagnosis and treatment, yet its clinical translation still faces challenges such as high technical cost and intratumoral heterogeneity. In the future, relying on artificial intelligence, liquid biopsy, and other technologies, clinically practical subtype-guided individualized therapeutic strategies can be realized.

Citation： ZHANG Songtao, GUO Weihan, SHI Anni, ZHU Zhengyu, WANG Guihua. Research progress on molecular classification of gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(5): 635-647. doi: 10.7507/1007-9424.202604097 Copy

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5. Chia NY, Tan P. Molecular classification of gastric cancer. Ann Oncol, 2016, 27(5): 763-769.
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8. Cristescu R, Lee J, Nebozhyn M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med, 2015, 21(5): 449-456.
9. Smyth E, Nilsson M, Grabsch H, et al. Gastric cancer. Lancet, 2020, 396(10251): 635-648.
10. Ma H, Srivastava S, Ho SWT, et al. Spatially resolved tumor ecosystems and cell states in gastric adenocarcinoma progression and evolution. Cancer Discov, 2025, 15(4): 767-792.
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22. Li Y, Yang Y, Lu Y, et al. Predictive value of CHFR and MLH1 methylation in human gastric cancer. Gastric Cancer, 2015, 18(2): 280-287.
23. Balgkouranidou I, Matthaios D, Karayiannakis A, et al. Prognostic role of APC and RASSF1A promoter methylation status in cell free circulating DNA of operable gastric cancer patients. Mutat Res, 2015, 778: 46-51.
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31. 陸懿, 張琪, 肖瑤, 等. 基于程序性細胞死亡相關基因的胃癌分子亞型鑒定和預后模型構建. 現代生物醫學進展, 2025, 25(21): 3373-3386.
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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Research progress on molecular classification of gastric cancer

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