ArticleTranslational oncology2026
Single-Cell sequencing investigation of endoplasmic reticulum stress-related genes in gastric cancer prognostic models and identification of NOX5 as a novel therapeutic target.
Article in Translational 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 cancer (GC) has a poor prognosis, and its pathogenesis remains incompletely understood. Endoplasmic reticulum stress (ERS) may influence GC progression, yet ERS-based prognostic models are lacking. We aimed to develop an ERS-related prognostic signature using single-cell analysis and identify potential therapeutic targets.
methodsIntegrated analyses including single-cell RNA sequencing, cell‒cell communication, GSVA enrichment, and drug sensitivity inference were performed. A 14-gene prognostic model was constructed using Cox regression and LASSO, and validated via Kaplan-Meier and ROC curves. NOX5 function was assessed through in vitro proliferation and migration assays.
resultsThe ERS signature outperformed clinicopathological parameters in predicting GC survival, with AUCs of 0.75, 0.71, and 0.64 for 1-, 3-, and 5-year OS, respectively. Patients were stratified into high- and low-risk groups with distinct immune checkpoint profiles. NOX5, the top risk gene (HR > 2.0), was upregulated in GC, and its knockdown significantly suppressed AGS and MKN-45 cell proliferation and migration (p < 0.01).
conclusionThe ERS-related signature is a promising independent prognostic and predictive biomarker for GC. NOX5 represents a novel potential therapeutic target.
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