VCAM-1 predicts poor prognosis and modulates immune infiltration in gastric cancer: a TCGA-based bioinformatics study

Background Gastric cancer (GC) is a leading cause of cancer-related mortality; however, biomarkers predicting its immunotherapy resistance remain scarce. Vascular cell adhesion molecule ( VCAM )- 1 , an immune cell adhesion mediator, is implicated in tumor progression; however, its prognostic and immunomodulatory roles in GC remain unclear. Methods In this study, we analyzed VCAM-1 expression and its clinical relevance in GC using RNA-sequencing data from The Cancer Genome Atlas. Differential gene analysis, gene set enrichment analysis (GSEA), and single-sample GSEA were used to identify the underlying pathways and immune infiltration patterns. Validation was performed via Cox regression, receiver operating characteristic, and immunohistochemical (Human Protein Atlas database) analyses. Results VCAM-1 expression levels were significantly upregulated in the GC tissues (p < 0.001) and correlated with advanced T stage (p = 0.046), N stage (p = 0.047), and poor overall survival (hazard ratio = 1.54; p = 0.046). GSEA linked VCAM-1 expression to various immune pathways (e.g., interleukin-17 signaling), and single-sample GSEA revealed its positive associations with the Th1, cytotoxic, and CD8 + T cell proportions (p < 0.05) and inverse correlation with the Th17 cell proportion. Immunohistochemistry revealed elevated VCAM-1 protein levels in the tumors. Conclusion VCAM-1 is a novel prognostic biomarker driving immunosuppressive microenvironmental remodeling in GC. Furthermore, its dual roles in immune regulation highlight its potential to optimize GC immunotherapy.