Advanced Stage, High-Grade Primary Tumor Ovarian Cancer: A Multi-Omics Dissection and Biomarker Prediction Process

Abstract Ovarian cancer (OC) incidence and mortality rates are estimated to increase globally in the years to come. Early diagnosis of OC is still one of the most significant challenges facing researchers due to extensive metastases and the lack of recognition of biomarkers in advanced stages of high-grade primary tumors (HGPTs). In this study, OC cell lines were analyzed using bioinformatics study and gene expression screening, utilizing Gene Expression Omnibus (GEO) the microarray dataset with 53 HGPTs and 10 normal samples were analyzed by using GEO2r to figure out differently-expressed genes (DEGs). Subsequently, Gene set enrichment analysis (GSEA), ChIP enrichment analysis (ChEA), eXpression2Kinases (X2K), and Human Protein Atlas (HPA) were used to analyze signaling pathways, transcription factors (TFs), kinases, and proteome analysis, respectively. Protein-protein interaction (PPI) networks were made by using STRING and Cytoscape Software. Co-expression and hub genes were determined via STRING database and cytoHubba plug-in, and DEGs were confirmed by using gene expression profiling interactive analysis (GEPIA). KIAA0101, RAD51AP1, FAM83D, CEP55, PRC1, CKS2, CDCA5, NUSAP1, ECT2 and TRIP13 were found to be the top 10 hub genes. At the same time, SIN3A, VDR, TCF7L2, NFYA, and FOXM1 were identified as the top 5 TFs in HGPT. Ultimately, the clustering of hub genes was carried out using the available tools in the protein atlas server, based on which 5 out of 10 candidate genes, including CEP55, PRC1, CKS2, CDCA5 and NUSAP1, were chosen as markers. miRNAs analysis showed that hsa-miR-215-5p, hsa-miR-193b-3p, hsa-miR-192-5p and could target the largest number of HGPT genes. Collectively, HGPT-related genes, especially hub genes, TFs, miRNAs and pathways seem to have a great potential as novel biomarkers for HGPT as well as diagnosis and treatment strategies in OC.