Abstract
BackgroundOvarian cancer (OC) ranks fifth as a cause of gynecological cancer-associated death globally. Until now, the molecular mechanisms underlying the tumorigenesis and prognosis of OC have not been fully understood. This study aims to identify hub genes and therapeutic drugs involved in OC.MethodsFour gene expression profiles (GSE54388, GSE69428, GSE36668, and GSE40595) were downloaded from the Gene Expression Omnibus (GEO), and the 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 were first identified by GEO2R and FunRich software. Next, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were performed for functional enrichment analysis of these DEGs. Then, the hub genes were identified by the cytoHubba plugin and the other bioinformatics approaches including protein-protein interaction (PPI) network analysis, module analysis, survival analysis, and miRNA-hub gene network construction was also performed. Finally, the GEPIA2 and DGIdb databases were utilized to verify the expression levels of hub genes and to select the candidate drugs for OC, respectively.ResultsA total of 171 DEGs were identified, including 114 upregulated and 57 downregulated DEGs. The results of the GO analysis indicated that the upregulated DEGs were mainly involved in cell division, nucleus, and protein binding, whereas the biological functions showing enrichment in the downregulated DEGs were mainly negative regulation of transcription from RNA polymerase II promoter, protein complex and apicolateral plasma membrane, and glycosaminoglycan binding. As for the KEGG-pathway, the upregulated DEGs were mainly associated with metabolic pathways, biosynthesis of antibiotics, biosynthesis of amino acids, cell cycle, and HTLV-I infection. Additionally, 10 hub genes (KIF4A, CDC20, CCNB2, TOP2A, RRM2, TYMS, KIF11, BIRC5, BUB1B, and FOXM1) were identified and survival analysis of these hub genes showed that OC patients with the high-expression of CCNB2, TYMS, KIF11, KIF4A, BIRC5, BUB1B, FOXM1, and CDC20 were statistically more likely to have poorer progression free survival. Meanwhile, the expression levels of the hub genes based on GEPIA2 were in accordance with those based on GEO. Finally, DGIdb database was used to identify 62 small molecules as the potentially targeted drugs for OC treatment.ConclusionsIn summary, the data may produce new insights regarding OC pathogenesis and treatment. Hub genes and candidate drugs may improve individualized diagnosis and therapy for OC in future.
Highlights
Ovarian cancer (OC) ranks fifth as a cause of gynecological cancer-associated deaths globally [1], with an estimated 238,700 new cases and 151,900 deaths in 2012 [2]
Three of the datasets were from serous OC (SOC), and GSE40595 was from OC stroma (Table 1)
The Venn diagrams indicated that a total of 171 differentially expressed genes (DEGs) were identified from the four microarray profile datasets, including 114 upregulated genes and 57 downregulated genes in OC tissues compared to normal controls (Fig. 1 and Table 2)
Summary
Ovarian cancer (OC) ranks fifth as a cause of gynecological cancer-associated deaths globally [1], with an estimated 238,700 new cases and 151,900 deaths in 2012 [2]. The poor prognosis and high mortality can be mainly attributed to the lack of early and effective detection methods [5]. More efforts need to be invested towards the identification and understanding of novel biomarkers and specific targets of OC, which is considered the key to developing more effective diagnostic and therapeutic strategies. Ovarian cancer (OC) ranks fifth as a cause of gynecological cancer-associated death globally. The molecular mechanisms underlying the tumorigenesis and prognosis of OC have not been fully understood. This study aims to identify hub genes and therapeutic drugs involved in OC
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