Abstract
BACKGROUND: Colorectal cancer (CRC) is a major global health challenge, creating an urgent need to find new biomarkers that improve early detection and treatment success. While studies suggest that ANXA9 contributes to cancer development, its expression in CRC and its links to prognosis, immune evasion, and resistance are poorly understood. METHODS: This study conducted bioinformatics analysis of gene expression data from the TCGA and GEO to evaluate the prognostic and diagnostic potential of ANXA9. Kaplan-Meier survival analysis and ROC curves were employed to assess these capabilities. Furthermore, ANXA9 gene mutations were examined using cBioPortal, and promoter methylation levels were analyzed via UALCAN. Enrichment, immune infiltration, and treatment response analyses were also performed on ANXA9. RESULTS: Our research demonstrates that ANXA9 expression is significantly elevated in CRC tissues compared to normal tissues. This elevation is associated with pathological staging and TNM classification. Kaplan-Meier analysis reveals that increased ANXA9 levels are correlated with reduced overall survival and disease-specific survival. Furthermore, several mutations in ANXA9 have been identified, accompanied by a significant reduction in promoter methylation levels. Genes related to ANXA9 are significantly enriched in pathways involved in immune responses, such as cytokine secretion and T cell activation. We also observed a correlation between ANXA9 expression and the infiltration of immune cells, particularly M1 macrophages. ANXA9 expression is linked to increased levels of the immune checkpoint gene IGSF8 and resistance to chemotherapeutic agents. CONCLUSION: This study reveals the critical role of ANXA9 in colorectal cancer. Its increased expression is closely associated with poor prognosis, immune evasion, and chemotherapy resistance. This provides valuable evidence for future clinical research and treatment strategies.