Screening and verifying key genes with poor prognosis in colon cancer through bioinformatics analysis

Buyuan Dong; Mengyu Chai; Hao Chen; Qian Feng; Rong Jin; Sunkuan Hu

doi:10.21037/tcr-20-2309

Screening and verifying key genes with poor prognosis in colon cancer through bioinformatics analysis

Transl Cancer Res. 2020 Nov;9(11):6720-6732. doi: 10.21037/tcr-20-2309.

Authors

Buyuan Dong¹, Mengyu Chai², Hao Chen¹, Qian Feng¹, Rong Jin³, Sunkuan Hu¹

Affiliations

¹ Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Respiratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Epidemiology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Abstract

Background: Colon cancer (CC) is one of the tumors with high morbidity and mortality in the world, and has a trend of younger generation. The molecular level of CC has not been fully elaborated. The purpose of this study is to screen and identify important genes with poor prognosis and their mechanisms at different levels.

Methods: GSE74602 and GSE10972 gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. There were 58 normal tissues and 58 CC tissues. Differentially expressed genes (DEGs) were screened out by using the GEO2R tool and Venn diagram. Then, the DAVID online database was used to perform the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Six hub genes with the highest correlation were screened out after the modular analysis of the protein-protein interaction (PPI) network by using Cytoscape's MCODE plug-in. Finally, the overall survival of key hub genes and potential pathways were verified in GEPIA and UALCAN database.

Results: A total of 78 up-regulated DEGs were enriched in the mitotic nuclear division, cell division, cell proliferation, anaphase-promoting complex-dependent catabolic process and G2/M transition of the mitotic cell cycle. In total, 130 down-regulated DEGs were enriched in muscle contraction, bicarbonate transport, cellular response to zinc ion, negative regulation of growth, negative regulation of leukocyte apoptotic process and one-carbon metabolic process. CDK1, CCNB1, CDC20, AURKA, CCNA2 and TOP2A were the top six hub genes, mainly enriched in cell cycle pathways. Among them, CCNB1, CDK1, CDC20, CCNA2 were enriched in the G2/M phase. GEPIA and UALCAN database confirmed that CCNA2 and CCNB1 had a significant relationship with the poor prognosis of CC patients. Meanwhile, there was a positive correlation between the two.

Conclusions: Screening out genes with abnormal expression in CC help understand the initiation and progression of CC at the molecular level and explore candidate biomarkers for diagnosis, treatment and prognosis.

Keywords: Bioinformatical analysis; cell cycle; colon cancer (CC); correlation; differentially expressed gene (DEG); microarray.