Identification of common candidate genes and pathways for progression of ovarian, cervical and endometrial cancers

Abstract

Ovarian, cervical and endometrial cancers are the most common gynecological cancers affecting women worldwide. Overall, the molecular mechanism of the disease is not well understood. These cancers have similar embryological origin which has led to the hypothesis that they might share common genes and pathways for disease development. In order to find out pathways and key candidate genes shared by these three lethal gynecological cancers, we performed comparative gene expression analysis for the three types of cancers using microarray data. Differentially expressed genes (DEGs) were identified by the combination of |log2fc| > 1 and adjusted p (padj) value<0.05. Our analysis revealed a set of 426 genes in ovarian cancer (OC), 128 common genes in cervical cancer (CC), and 288 genes in endometrial cancer (EC) were differentially expressed. Gene ontology (GO) and pathway enrichment analysis of the DEGs showed that cell cycle and p53 signaling pathways were conserved across the three cancer types. We constructed co-expression network of the DEGs and identified a subset of eight common genes namely ASPM, CEP55, ECT2, KIF4A, MELK, RRM2, TOP2A, and TTK that were differentially co-expressed in all the three cancer types formed a core circuitry called key candidate genes. Identified candidate genes were validated by using gene expression profiling interactive analysis (GEPIA) tool and found the candidate genes were highly expressed in OC, CC and EC compared to the respective normal tissues. Involvement of the candidate genes in the cancer progression were further supported by literature survey that might provide new insights on the prognosis and treatment strategies for the three female-specific cancers.