Melanoma Cell Adhesion Molecule Plays a Pivotal Role in Proliferation, Migration, Tumor Immune Microenvironment, and Immunotherapy in Colorectal Cancer.

INTRODUCTION: MCAM, alternatively referred to as CD146, is an integral membrane glycoprotein belonging to the immunoglobulin superfamily. However, its importance in the tumorigenesis of colorectal cancer is still partially understood. Therefore, this study was designed to investigate the significance of MCAM in colorectal cancer. METHODS: MCAM expression was analyzed by TCGA and GEO databases. qRT-PCR and IHC analysis were conducted to validate MCAM expression in patient tissues. The tumor-inhibiting ability of MCAM was further assessed by CCK-8 assay, colony formation assay, and wound-healing assay. qRT-PCR and WB analysis were conducted to evaluate the expression of EMT markers and MMP2/9. qRT-PCR analysis was utilized to detect the polarization status of macrophages. Kaplan-Meier curve, univariate, and multivariate cox analyses were employed to verify the ability of MCAM in prognosis prediction. TIDE scores were used to assess the impact of MCAM on immunotherapy. RESULTS: The expression of MCAM was significantly downregulated in CRC, and low MCAM expression revealed poor prognosis in CRC patients. Moreover, MCAM overexpression inhibited the proliferation, migration, and invasive ability of CRC cells. Additionally, MCAM overexpression suppressed N-cadherin and MMP2/9 expression. Furthermore, MCAM impacted M1 macrophage polarization. MCAM is an independent predictor of CRC patient prognosis through Cox regression analysis. Lastly, TIDE score analysis indicated that elevated expression of MCAM increased immunotherapy efficacy. CONCLUSION: The findings of this research suggest that MCAM impacts M1 macrophage polarization and enhances immunotherapy efficacy, underscoring its potential as a therapeutic target for colorectal cancer.