Language

English

Publication Date

5-19-2026

Journal

Cell Reports Medicine

DOI

10.1016/j.xcrm.2026.102756

PMID

42013851

PMCID

PMC13198309

PubMedCentral® Posted Date

4-20-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Gastric cancer is marked by profound molecular and microenvironmental heterogeneity that limits therapeutic progress. Here, we present a 15-layer multi-omics atlas that integrates genomics, epigenomics, transcriptomics, proteomics, multiple post-translational modifications (PTMs), protein-protein interactions, metabolomics, and microbiome profiles from 159 primary gastric adenocarcinomas and 30 matched normal adjacent tissues. Using cell-state deconvolution, we define tumor ecotypes that refine genomic and histological subtypes by capturing distinct tumor microenvironment architectures linked to clinical outcomes and potential associations with immunotherapy response. Multi-omics integration prioritizes genomic and epigenomic aberrations and their associated vulnerabilities; defines ecotype-specific transcriptional programs, signaling pathways, PTMs, protein interaction networks, and metabolic regulation; and identifies microbiome features linked to ecotypes and resistance pathways. We further prioritize ecotype-, genomic subtype-, and cell type-specific targetable proteins using proteomic and PTM analyses within a tumor microenvironment context. This comprehensive atlas provides a systems-level blueprint for decoding gastric cancer heterogeneity and advancing precision oncology.

Keywords

Humans, Stomach Neoplasms, Multiomics, Tumor Microenvironment, Proteomics, Metabolomics, Protein Processing, Post-Translational, Genomics, Gene Expression Regulation, Neoplastic, Protein Interaction Maps, Microbiota, gastric cancer, multi-omics, tumor ecotypes, tumor microenvironment, proteogenomics, post-translational modifications, protein-protein interactions, metabolomics, microbiome, precision oncology, therapeutic targets

Published Open-Access

yes

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