Differential Expression of HIF1A, EPAS1, and VEGF Genes in Benign and Malignant Ovarian Neoplasia.

Abstract

Simple SummaryOvarian cancer (OC) has the highest mortality rate of all gynecological malignancies. Moreover, at the time of the first clinical manifestation, most patients have an advanced stage of the disease. Our study examined differences in mRNA levels of hypoxia-inducible factor 1-alpha (HIF1A); endothelial PAS domain protein 1, also known as hypoxia-inducible factor 2-alpha (HIF2A/EPAS1); and vascular endothelial growth factor A (VEGFA) between cancerous tissue, benign hyperplastic changes in the ovary, and normal tissue. We found that gene expression changes were visible not only in the case-control study, but also along with changes in severity. We observed disturbances in the expression levels of interdependent genes. Our findings suggest that mutual association in the expression of both HIF1A and HIF2A/EPAS1 with VEGFA has prognostic importance for patients with OC. Our observations may help identify patients for clinical trials aimed at inhibiting the hypoxia-induced neovascularization-dependent pathways.Ovarian cancer (OC) has the highest mortality rate of all gynecological malignancies. Moreover, at the time of the first clinical manifestation, most patients have an advanced stage of the disease. Our study examined differences in mRNA levels of hypoxia-inducible factor 1-alpha (HIF1A); endothelial PAS domain protein 1, also known as hypoxia-inducible factor 2-alpha (HIF2A/EPAS1); and vascular endothelial growth factor A (VEGFA) between cancerous tissue, benign hyperplastic changes in the ovary, and normal tissue. Our cohorts consisted of 52 patients diagnosed with OC (n = 55), benign non-cancerous changes (n = 21), and normal tissue samples (n = 38). The mRNA expression level was evaluated using RT-qPCR. We found that gene expression changes were visible not only in the case-control study, but also along with changes in severity. Additionally, the gene expression was differentiated in age, BMI, menopausal status, and the number of comorbidy-related groups. Furthermore, our findings demonstrate that analyzing the correlation between genes is essential. In a case-to-case and case-to-control study, we observed disturbances in the expression levels of interdependent genes. Our findings suggest that mutual association in the expression of both HIF1A and HIF2A/EPAS1 with VEGFA has prognostic importance for patients with OC. Our observations may help identify patients for clinical trials aimed at inhibiting the hypoxia-induced neovascularization-dependent pathways.