Comprehensive analysis of location-specific hub genes related to the pathogenesis of colon cancer.

Abstract

The molecular mechanisms underlying colon cancer lesions at different sites are not entirely clear. Herein, we aimed to explore location-specific gene profiles related to the pathogenesis of colon cancer and to identify their function. The robust rank aggregation (RRA) method was used to integrate colon cancer microarray datasets and screen differentially expressed gene (DEG) profiles between left- and right-sided colon cancers. Then, weighted gene co-expression network analysis (WGCNA) was performed to cluster the DEGs into modules and identify hub genes. The selected hub genes were validated using The Cancer Genome Atlas dataset and clinical tissues. We assessed the association of selected hub genes with the methylation status in immune cells. In total, 905 DEGs were identified by RRA; five gene modules and 18 hub genes were related to the clinical traits of colon cancer by WGCNA. Four hub genes were selected and shown to be associated with colon cancers on different sides and distant metastasis in the validation analysis. The four hub genes showed a low methylation status, and their expression was significantly associated with methylation status. Positive correlations were observed between the four hub genes and tumor purity and among the four types of immune cells. Gene set enrichment analysis revealed that the four hub genes were mainly involved in two cancer-related pathways. In conclusion, this study identified a set of location-specific genes related to the pathogenesis of colon cancer. These four hub genes may act as novel candidate targets for the treatment of colon cancer.