ArticleTranslational cancer research2026
A stromal-derived five-gene signature predicts gastric cancer recurrence through integrated bioinformatics and single-cell analysis.
Article in Translational cancer research, 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
Background: Gastric cancer (GC) remains a major cause of cancer-related mortality worldwide, with recurrence rates exceeding 40% following curative resection. While molecular profiling has revealed GC heterogeneity, computational approaches integrating tumor microenvironment (TME) characteristics for prognostic assessment remain underexplored. Therefore, this study aimed to develop and validate a stromal-derived gene signature for predicting gastric cancer recurrence and to characterize its tumor-microenvironmental and cell-type specificity through integrated bulk transcriptomic, machine-learning, and single-cell analyses. Methods: Using publicly available datasets, we developed a prognostic signature through bootstrap-based feature selection (1,000 iterations) using 279 GC patients from GSE62254, divided into training (n=196) and validation (n=83) cohorts. Weighted gene co-expression network analysis (WGCNA) identified recurrence-associated modules. Single-cell RNA sequencing (scRNA-seq) of 43,560 cells determined cell-type specificity. Six machine learning algorithms assessed predictive performance. External validation used The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), including 419 patients with complete risk-score data, and pan-cancer cohorts (n=9,328 across 33 cancer types). Results: The five-gene signature ( Conclusions: This stromal-derived five-gene signature suggests that microenvironment composition is strongly associated with GC recurrence, independent of tumor-intrinsic mutational burden. The predominant stromal expression and independence from TMB indicate that prognostic value derives from stromal-tumor interactions rather than tumor cell-autonomous features. While experimental validation is required to establish causality, these findings identify the stromal compartment as a potential therapeutic target and highlight the importance of integrating microenvironment characteristics into prognostic assessment.
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