An Anoikis‐Related Gene Signature Associated With Stromal Remodeling and Clinical Outcome in Gastric Cancer

ABSTRACT

Gastric cancer (GC) remains a highly aggressive malignancy with poor prognosis. Anoikis resistance is closely associated with tumor progression and metastasis, but the prognostic and functional relevance of anoikis‐related genes (ARGs) in GC remains incompletely understood. Public transcriptomic, clinical, somatic mutation, and single‐cell RNA sequencing (scRNA‐seq) datasets were integrated to identify differentially expressed ARGs, develop an ARG‐based risk model, and investigate its associations with tumor microenvironment (TME) features. In vitro experiments were performed to assess the effects of selected candidate genes on GC cell migration and invasion. Forty‐five differentially expressed ARGs were identified in The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA‐STAD) cohort. An ARG‐based risk model was developed using the TCGA‐STAD cohort and evaluated in the GSE84437 cohort. The model was associated with overall survival and provided potential value for risk stratification, although its discriminative performance was modest. High‐risk patients showed distinct immune, stromal, and somatic mutational features. Single‐cell analysis suggested that ARG‐related transcriptional programs were associated with stromal remodeling and endothelial‐to‐mesenchymal transition (EndMT)‐associated features in the GC microenvironment. Among the core ARGs, EEF1A2 and TAGLN showed prognostic relevance and higher protein expression in GC tissues. Small interfering RNA (siRNA)‐mediated knockdown of either gene reduced the migration and invasion of HGC‐27 cells. These findings indicate that ARG‐related molecular features are associated with GC prognosis and immune‐stromal characteristics, while EEF1A2 and TAGLN may represent candidate genes related to GC cell migration and invasion.