Identification of Novel Genes and Pathways of Ovarian Cancer Using a Comprehensive Bioinformatic Framework.

Abstract

Ovarian cancer (OC) is a significant contributor to gynecological cancer-related deaths worldwide, with a high mortality rate. Despite several advances in understanding the pathogenesis of OC, the molecular mechanisms underlying its development and prognosis remain poorly understood. Therefore, the current research study aimed to identify hub genes involved in the pathogenesis of OC that could serve as selective diagnostic and therapeutic targets. To achieve this, the dataset GEO2R was used to retrieve differentially expressed genes. The study identified a total of five genes (CDKN1A, DKK1, CYP1B1, NTS, and GDF15) that were differentially expressed in OC. Subsequently, a network analysis was performed using the STRING database, followed by the construction of a network using Cytoscape. The network analyzer tool in Cytoscape predicted 276 upregulated and 269 downregulated genes. Furthermore, KEGG analysis was conducted to identify different pathways related to OC. Subsequently, survival analysis was performed to validate gene expression alterations and predict hub genes, using a p-value of 0.05 as a threshold. Four genes (CDKN1A, DKK1, CYP1B1, and NTS) were predicted as significant hub genes, while one gene (GDF15) was predicted as non-significant. The adjusted P values of said predicted genes are 2.85E - 07, 5.49E - 06, 4.28E - 07, 1.43E - 07, and 3.70E - 07 for CDKN1A, DKK1, NTS, GDF15, and CYP1B1 respectively; additionally 6.08, 5.76, 5.74, 5.01, and 4.9 LogFc values of the said genes were predicted in GEO data set. In a boxplot analysis, the expression of these genes was analyzed in normal and tumor cells. The study found that three genes were highly expressed in tumor cells, while two genes (CDKN1A and DKK1) were more elevated in normal cells. According to the boxplot analysis for CDKN1A, 50% of tumor cells ranged between approx 3.8 and 5, while 50% of normal cells ranged between approx 6.9 and 7.9, which is greater than tumor cells. This shows that in normal cells, the CYP1B1 has a high expression level according to the GEPIA boxplot; addtionally the boxplot for DKK1 indicated that 50% of tumor cells ranged between approx 0 and 0.5, which was less than that of normal cells which ranged between approx 0.3 and 0.9. It shows that DKK1 is highly expressed in normal genes. Overall, the current study provides novel insights into the molecular mechanisms underlying OC. The identified hub genes and drug candidate targets could potentially serve as alternative diagnostic and therapeutic options for OC patients. Further research is needed to investigate the clinical significance of these findings and develop effective interventions that can improve the prognosis of patients with OC.