Comprehensive Analysis of Subtype-Specific Molecular Characteristics of Colon Cancer: Specific Genes, Driver Genes, Signaling Pathways, and Immunotherapy Responses

Abstract

Colon cancer is a complex, heterogeneous disease. The Colorectal Cancer Subtyping Consortium reported a novel classification system for colon cancer in 2015 to better understand its heterogeneity. This molecular classification system divided colon cancer into four distinct consensus molecular subtypes (CMS 1, 2, 3, and 4). However, the characteristics of different colon cancer molecular subtypes have not been fully elucidated. This study comprehensively analyzed the molecular characteristics of varying colon cancer subtypes using multiple databases and algorithms, including The Cancer Genome Atlas (TCGA) database, DriverDBv3 database, CIBERSORT, and MCP-counter algorithms. We analyzed the alterations in the subtype-specific genes of different colon cancer subtypes, such as the RNA levels and DNA alterations, and showed that specific subtype-specific genes significantly affected prognosis. We also explored the changes in colon cancer driver genes and representative genes of 10 signaling pathways in different subtypes. We identified genes that were altered in specific subtypes. We further detected the infiltration of 22 immune cell types in four colon cancer subtypes and the infiltration level of primary immune cells among these subtypes. Additionally, we explored changes in immune checkpoint genes (ICGs) and immunotherapy responses among different colon cancer subtypes. This study may provide clues for the molecular mechanism of tumorigenesis and progression in colon cancer. It also offers potential biomarkers and targets for the clinical diagnosis and treatment of different colon cancer subtypes.