Application of Bioinformatics Analysis to Identify Important Pathways and Hub Genes in Ovarian Cancer Affected by WT1

Abstract

Wilms tumor gene (WT1) is used as a marker for the diagnosis and prognosis of ovarian cancer. However, the molecular mechanisms involving WT1 in ovarian cancer require further study. Herein, we used bioinformatics and other methods to identify important pathways and hub genes in ovarian cancer affected by WT1. The results showed that WT1 is highly expressed in ovarian cancer and is closely related to the overall survival and progression-free survival (PFS) of ovarian cancer. In ovarian cancer cell line SKOV3, WT1 downregulation increased the mRNA expression of 638 genes and decreased the mRNA expression of 512 genes, which were enriched in the FoxO, AMPK, and the Hippo signaling pathways. The STRING online tool and Cytoscape software were used to construct a Protein-protein interaction (PPI) network and for Module analysis, and 18 differentially expressed genes (DEGs) were selected. Kaplan-Meier plotter analysis revealed that 16 of 18 genes were related to prognosis. Analysis of GEPIA datasets indicated that 7 of 16 genes were differentially expressed in ovarian cancer tissues and in normal tissues. The expression of IGFBP1 and FBN1 genes increased significantly after WT1 interference, while the expression of the SERPINA1 gene decreased significantly. The correlation between WT1 expression and that of these three genes was consistent with that of ovarian cancer tissues and normal tissues. According to the GeneMANIA online website analysis, there were complex interactions between WT1, IGFBP1, FBN1, SERPINA1, and 20 other genes. In conclusion, we have identified important signaling pathways involving WT1 that affect ovarian cancer, and distinguished three differentially expressed genes regulated by WT1 associated with the prognosis of ovarian cancer. Our findings provide evidence outlining mechanisms involving WT1 gene expression in ovarian cancer and provides a rational for novel treatment of ovarian cancer.