COL4A1 as a potential prognostic biomarker with functional roles in colon cancer progression

COL4A1, a key component of the basement membrane, has been increasingly implicated in tumor progression, yet its role in colon cancer remains incompletely understood. In this study, we conducted a comprehensive integrative analysis using transcriptomic data from the TCGA-COAD cohort, combined with functional validation in colon cancer cell lines. Gene set enrichment analysis (GSEA) revealed that high COL4A1 expression was associated with oncogenic pathways including epithelial-mesenchymal transition (EMT), KRAS signaling, and inflammatory responses. Immune infiltration analysis indicated that COL4A1 expression negatively correlated with CD8⁺ T cell infiltration but positively correlated with macrophage subtypes. Immunophenoscore (IPS) analysis further revealed that tumors with high COL4A1 expression exhibited significantly higher IPS values, suggesting altered immunogenicity. Functional assays demonstrated that COL4A1 knockdown reduced cell proliferation, migration, and invasion in vitro. Co-expression analysis of EMT markers showed strong positive correlations between COL4A1 and mesenchymal genes such as VIM, ZEB1, SNAI1, and FN1, supporting its role in EMT-like phenotypes. Collectively, our findings suggest that COL4A1 may serve as a prognostic biomarker and contributor to tumor progression and immune remodeling in colon cancer.