Identification of novel biomarkers in prostate cancer diagnosis and prognosis.

Abstract

Prostate cancer (PCa) is a common urinary malignancy. The lack of specific and sensitive biomarkers for the early diagnosis and prognosis of PCa makes it important to seek alternatives.R software was used to analyze the PCa expression profile from data sets in Gene Expression Omnibus. Core differential genes were identified by String and Cytoscape and further validated by Gene Expression Profiling Interactive Analysis (GEPIA) and The Human Protein Atlas(HPA). Gene Ontologyanalysis was done in the DIVID database and visualization analysis was conducted by Hiplot. Pathway enrichment was analyzed by IPA. To identify potential competitive endogenous RNAs(ceRNA) networks, the experimentally validated microRNA-target interactions database(miRTarBase), The Encyclopedia of RNA Interactomes (StarBase), lncBase, and GEPIA were used. The lncLocator was utilized to perform subcellular localization of longnoncoding RNAs(lncRNAs). Both miRTarBase and StarBase were used to find the binding site of mRNAs-miRNAs and miRNAs-lncRNAs. Visualization of the ceRNA network was performed with Cytoscape.Nine genes closely related to the diagnosis and prognosis of PCa were obtained, including four identified biomarkers by HPA, CENPF, TPX2, TK1, and CCNB1, and five novel PCa biomarkers, RRM2, UBE2C, TOP2A, BIRC5, and ZWINT. Pathway analysis indicated that PCa carcinogenesis was highly correlated with liver fibrosis pathways, ILK signaling, and NRF2-mediated oxidative stress response. Two sets of ceRNA networks,BIRC5/hsa-miR-218-5p/NEAT1and UBE2C/hsa-miR-483-3p/NEAT1 were found to be novel biomarkers for the identification of PCa. The quantitative real-time polymerase chain reactionresults verified that UBE2C, BIRC5, and NEAT1 were upregulated and hsa-miR-218-5p and hsa-miR-483-3p were downregulated in human PCa cells compared with normal prostate epithelial cells.The novel identified biomarkers in this study would be valuable for the diagnosis and prognosis of PCa.