Identification of gene modules and hub genes in colon adenocarcinoma associated with pathological stage based on WGCNA analysis

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality in the world, in which colon adenocarcinoma (COAD) is the most common histological subtype of CRC. In this study, our aim is to identify gene modules and representative candidate biomarkers for clinical prognosis of patients with COAD, and help to predict prognosis and reveal the mechanisms of cancer progression. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network and identify gene modules correlated with TNM clinical staging of COAD patients. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with the module gene. Protein-protein interaction (PPI) network and hub gene identification were explored with Cytoscape software. Finally, the hub gene mRNA level was validated in Oncomine database. Five gene modules, related with the pathological TNM stage, were constructed, and the gene module was enriched in cell proliferation, invasion and migration related GO terms and metabolic related KEGG pathways. A total of top 10 hub genes was identified, and in which six of the hub genes show a significant up-regulation in COAD as compared to normal tissue, including IVL, KRT16, KRT6C, KRT6A, KRT78 and SBSN. In conclusion, we identified five gene modules and six candidate biomarkers correlated with the TNM staging of COAD patients. These findings may help us to understand the tumor progression of COAD and provide prognostic biomarkers as well as therapeutic targets.

Keywords: COAD; Gene modules; Hub genes; TNM; WGCNA.