CSMD1 mutation is associated with prognosis, tumor mutation burden, and immunophenotype in non-metastatic colorectal cancer

Abstract

Abstract Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Comprehensive clinical management and precise treatment for CRC patients are very important, which can significantly improve the survival rates of patients, especially those who have not developed distant metastases. The study is aimed to explore the relationship of somatic mutations with immune response and prognosis in non-metastatic CRC (non-mCRC) patients. We collected gene expression data, clinical information, and somatic mutation data from The Cancer Genome Atlas and the International Cancer Genome Consortium databases. We identified 16 mutated genes associated with non-mCRC that were common to both databases and calculated the tumor mutation burden (TMB). Kaplan-Meier survival analysis indicated that of the 16 mutant genes, CUB and Sushi multiple domains 1 (CSMD1) mutations are related to CRC prognosis, and this was confirmed by univariable and multivariable Cox regression analyses. Finally, we used gene set enrichment analysis (GSEA) to explore the association of CSMD1 mutations with immune response pathways, and also measured the tumor-infiltrating immune cell fractions and the key immune checkpoints expression. The results indicated that the CSMD1 mutation might activate the non-mCRC immune response. Thus, CSMD1 might be regarded as a promising biomarker to predict immune response in non-mCRC.