COL1A2 expression is associated with prognosis, stromal remodeling, and predicted immunotherapy response in gastric cancer

Background COL1A2 encodes type I collagen alpha2 chain, a stromal component in gastric cancer (GC); its prognostic value, cellular origin, and immune microenvironment relation remain unclear. Methods We analyzed TCGA-STAD, GSE63089, and ACRG GSE62254. Associations between COL1A2 abundance and overall survival (OS), clinicopathology, pathways, and tumor microenvironment were assessed. High/low groups by median expression. Two Cox models used pathological stage or separate T/N/M. Immunotherapy response predicted via TIDE and IPS. WGCNA, PPI, and LASSO with five ECM genes, ten-fold cross-validation and 200 repeats, were applied. qPCR and Western blot measured mRNA and protein in seven paired tissues. Results COL1A2 was higher in GC and linked to poorer OS, but time-dependent AUCs were 0.60, 0.65, 0.66. In ACRG, OS association was not significant (HR 1.83, P = 0.085). Per SD increase, adjusted HR was 1.21 (stage model, P = 0.036) and 1.14 (T/N/M model, P = 0.171). C-index gains were only 0.006 and 0.003. Higher abundance correlated with stroma-rich microenvironment and M2 macrophage infiltration. TIDE/IPS predicted lower ICI response probability. LASSO selected SPARC, ELN, and BGN stably. Tumor tissues showed higher mRNA and protein. Conclusions COL1A2 associates with poor prognosis, stromal remodeling, and predicted immunotherapy response, but its prognostic effect varies between models and discrimination improvement is small.