Background: This study aimed to identify the hub genes associated with prognosis of patients with ovarian cancer by using integrated bioinformatics analysis and experimental validation.
Methods: Four microarray datasets (GSE12470, GSE14407, GSE18521 and GSE46169) were analyzed by the GEO2R tool to screen common differentially expressed genes (DEGs). Gene Ontology, the Kyoto Encyclopedia of Genes and Genomes, the (KEGG) pathway and Reactome pathway enrichment analysis, protein–protein interaction (PPI) construction, and the identification of hub genes were performed. Furthermore, we performed the survival and expression analysis of the hub genes. In vitro functional assays were performed to assess the effects of hub genes on ovarian cancer cell proliferation, caspase-3/7 activity and invasion.
Results: A total of 89 common DEGs were identified among these four datasets. The KEGG and Reactome pathway results showed that the DEGs were mainly associated with cell cycle, mitotic and p53 signaling pathway. A total of 20 hub genes were identified from the PPI network by using sub-module analysis. The survival analysis revealed that high expression of six hub genes (AURKA, BUB1B, CENPF, KIF11, KIF23  and TOP2A ) were significantly correlated with shorter overall survival and progression-free survival of patients with ovarian cancer. Furthermore, the expression of the six hub genes were validated by the GEPIA database and Human Protein Atlas, and functional studies revealed that knockdown of KIF11  and KIF23  suppressed the SKOV3 cell proliferation, increased caspase-3/7 activity and attenuated invasive potentials of SKOV3 cells. In addition, knockdown of KIF11  and KIF23  up-regulated E-cadherin mRNA expression but down-regulated N-cadherin and vimentin mRNA expression in SKOV3 cells.
Conclusion: Our results showed that six hub genes were up-regulated in ovarian cancer tissues and may predict poor prognosis of patients with ovarian cancer. KIF11  and KIF23  may play oncogenic roles in ovarian cancer cell progression via promoting ovarian cancer cell proliferation and invasion.
Keywords: ovarian cancer, bioinformatics, cell cycle, hub genes, survival, prognosis