Validation of a Macrophage Polarization-related Gene Signature-based Risk Model for Colorectal Cancer

Macrophage polarization significantly influences colorectal cancer (CRC) progression, yet prognostic models based on macrophage polarization-related genes (MPRGs) remain scarce. Utilizing TCGA and GEO databases, we established a 5-MPRG prognostic model through bioinformatics analysis. The model demonstrated significant differences in immune cell infiltration between high- and low-risk groups, with elevated Tregs, M0 and M2 macrophages in high-risk patients. Tumor microenvironment analysis revealed correlations between risk scores and immune checkpoint molecules, suggesting immunosuppressed TME contributes to poor prognosis. Drug sensitivity analysis identified differential responses between risk groups, with high-risk patients sensitive to 10 drugs (e.g., erlotinib) and low-risk patients to 22 drugs (e.g., dasatinib). Single-cell sequencing and immunohistochemistry validated TIMP1's elevated expression in CRC and its correlation with M2 macrophage markers (CD206, CD163). This study provides a robust prognostic tool for CRC while elucidating TIMP1's novel role in macrophage polarization and immunotherapy response.