ArticleDiscover oncology2026
Identification of a biologically coherent three gene immune signature predictive of immunotherapy benefit in gastric adenocarcinoma.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundGastric adenocarcinoma (GAC) exhibits marked interpatient heterogeneity. Compact, biologically interpretable signatures linked to tumor-immune contexture may aid reproducible risk stratification and hypothesis generation for therapeutic responsiveness.
methodsTCGA-GAC RNA-seq (n = 407; 375 tumors, 32 normals) was analyzed with limma to identify DEGs (p < 1 × 10⁻³, |log₂FC|>1). ImmPort overlap yielded immune DEGs, which were interaction-expanded via STRING to construct an immune-enriched candidate set for unsupervised co-expression analysis. WGCNA on expressed candidates identified co-expression modules; modules most associated with the tumor phenotype were prioritized for network centrality analysis, survival screening (maxstat), and multivariable Cox modeling to derive an immune-related gene prognostic index (IRGPI).
resultsXRCC2, NUSAP1, and ZWILCH were retained as independent prognostic factors and combined into IRGPI (0.526·XRCC2 + 0.581·NUSAP1 - 0.498·ZWILCH). IRGPI significantly stratified overall survival in TCGA with modest discrimination (time-dependent AUC ≈ 0.55) and showed reproducible stratification in GSE26942 (AUC ≈ 0.63). CIBERSORT-based deconvolution identified three TME clusters with distinct survival patterns. IRGPI groups differed in in silico-inferred immunotherapy-related features (TIDE-derived metrics and PD-L1/MDSC/T-cell dysfunction signatures) and in predicted cisplatin/gemcitabine sensitivity by pRRophetic.
conclusionsThis three-gene IRGPI provides a compact, biologically anchored risk stratification signal in GAC and is associated with computationally inferred immune contexture and therapy-related signatures. These associations are hypothesis-generating and require validation in treatment-annotated cohorts, particularly gastric cancer patients receiving immune checkpoint inhibitors; robustness to alternative gene-selection strategies should also be evaluated in future work.
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