Identification of hub genes and functional modules in colon adenocarcinoma based on public databases by bioinformatics analysis

J Gastrointest Oncol. 2021 Aug;12(4):1613-1624. doi: 10.21037/jgo-21-415.

Abstract

Background: Colon adenocarcinoma (COAD) is one of the most common cancers in the world. Although an extensive effort has been made to elucidate its pathogenesis, the underlying molecular mechanisms and genetic characteristics remain elusive.

Methods: In this study, protein-coding transcript expression profiles of COAD were downloaded from the Cancer RNA-Seq Nexus (CRN) database. They were then integrated to identify the overlapping transcripts expressed in every COAD RNA sequencing (RNA-seq) subset. The functional annotation of these overlapping genes (OLGs) involved noting their biological process (BP), cellular components (CC), molecular function (MF) for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway in the Database for Annotation, Visualization and Integrated Discovery (DAVID). Protein-protein interaction (PPI) networks were then constructed and analyzed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape 3.8.2.

Results: A total of 10 hub genes and 3 functional modules were screened by the plugin cytoHubba and MCODE, respectively. The plugin ClueGO and DAVID were used for the functional enrichment analyses of both hub genes and modules. The expression of hub genes was verified through the gene expression profiling interactive analysis (GEPIA) database. Survival analysis of the hub genes revealed that low expressions of ADCY5, GNG2, and PTPRC were significantly associated with an improved COAD prognosis. Furthermore, the expression level of ADCY5 in stages I/II was lower than that in stages III/IV, which seems to explain why the low expression of ADCY5 results in a better prognosis.

Conclusions: The identification of hub genes, functional modules, and pathways have the potential to improve our understanding of the causes and underlying molecular events of COAD. The hub gene ADCY5 could also be a prognostic monitoring indicator or therapeutic target in the treatment of COAD.

Keywords: Colon adenocarcinoma (COAD); bioinformatics analysis; colorectal cancer (CRC); protein-coding transcript.