Identification of B3GNT6 Gene Associated with Development of Colon Carcinoma by Weighted Gene Co-expression Network Analysis

Abstract

Colon cancer (COAD) stem cells are resistant to cancer treatment, so they are easy to lead to tumor progression after routine treatment failure. However, little is known about the molecular mechanism of cancer cells. The purpose of our study is to identify differential gene modules and representative candidate biomarkers for the clinical prognosis of patients, help to predict the prognosis and reveal the mechanism of cancer progression. In our study, based on the tumor Genome Atlas (TCGA) COAD database and gene expression profiles of GSE44076 from the Gene Expression Omnibus (GEO), the differentially co-expressed genes in COAD and normal tissues were explored. Combined with weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis, 451 differential co-expression genes were screened out. As shown by functional annotation analysis using R clusterProfiler software package, these genes are mainly enriched in lipid catabolic process (biological process), cell apical part (cellular component) and phosphate hydrolase activity (molecular function). In addition, in the protein-protein interaction (PPI) network, 20 hub genes (ACAA2, FABP1, ACOX1, EHHADH, CPT2, ACADS, CPT1A, MT1G, MT1E, MT1X, MT1H, PPARGC1A, ACSS2, MT2A, MT1F, CRAT, UGT2B17, B3GNT6, and MUC4) were identified using Cytoscape's CytoHubba plug-in. Based on Kaplan–Meier univariate survival analysis and UALCAN database analysis, lower expression of B3GNT6 was associated with better overall survival (OS), which could greatly influence cancer development. Also, online TIMER and CIBERSORT database showed that there was a great correlation between high B3GNT6 gene expression and immune infiltrating cells in poor tumor progression. Finally, we verified the protein levels of B3GNT6 through HPA database. In conclusion, our study shows that B3GNT6 can play an important role in the progression of colon cancer and serve as potential biomarkers for future diagnosis and treatment.