Screening of hub genes and therapeutic drugs in ovarian cancer through bioinformatics

Ovarian cancer (OC) is the 6th most common cause of gynaecological cancer-related death worldwide. The molecular processes driving OC tumorigenesis and prognosis have remained unidentified. The goal of this research is to find hub genes and therapeutic medicines that are involved in OC. GEO2R and FunRich software were used to identify differentially expressed genes (DEGs) in OC tissues and normal tissues with an adjusted P-value 0.05 and a |log fold change (FC)| > 1.0 using four gene expression profiles (GSE54388, GSE69428, GSE36668, and GSE40595) downloaded from the Gene Expression Omnibus (GEO). Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were done for functional enrichment analysis of these DEGs. The hub genes were then discovered using the cytoHubba plugin and other bioinformatics techniques such as protein-protein interaction (PPI) network analysis, module analysis, survival analysis, and the development of a miRNA-hub gene network were used. Finally, the GEPIA2 and DGIdb databases were used to verify hub gene expression levels and select prospective medicines for OC, respectively.

There were 171 DEGs found in all, with 114 upregulated and 57 downregulated DEGs. The upregulated DEGs mainly were involved in cell division, nucleus, and protein binding. In contrast, the downregulated DEGs were primarily involved in negative regulation of transcription from the RNA polymerase II promoter, protein complex and apicolateral plasma membrane, and glycosaminoglycan binding, according to the GO analysis. The KEGG pathway’s increased DEGs were mainly connected with metabolic processes, antibiotic biosynthesis, amino acid biosynthesis, cell cycle, and HTLV-I infection.

Furthermore, 10 hub genes (KIF4A, CDC20, TOP2A, RRM2, TYMS, KIF11, BIRC5, BUB1B, FOXM1, and CDC20) were identified. Survival analysis of these hub genes revealed that OC patients with high expression of CCNB2, TYMS, KIF11, KIF4A, BIRC5, BUB1B, FOXM1, and CDC20 had statistically worse progression-free survival. Meanwhile, GEPIA2-based hub gene expression levels were comparable to GEO-based hub gene expression levels. Finally, the DGIdb database discovered 62 small compounds active to treat OC.

Reference

  1. Yang, D., He, Y., Wu, B. et al. Integrated bioinformatics analysis for the screening of hub genes and therapeutic drugs in ovarian cancer. J Ovarian Res 13, 10 (2020). https://doi.org/10.1186/s13048-020-0613-2.