Identification of Novel Diagnostic Biomarkers in Prostate Adenocarcinoma Based on the Stromal-Immune Score and Analysis of the WGCNA and ceRNA Network

Abstract

Prostate cancer is still a significant global health burden in the coming decade. Novel biomarkers for detection and prognosis are needed to improve the survival of distant and advanced stage prostate cancer patients. The tumor microenvironment is an important driving factor for tumor biological functions. To investigate RNA prognostic biomarkers for prostate cancer in the tumor microenvironment, we obtained relevant data from The Cancer Genome Atlas (TCGA) database. We used the bioinformatics tools Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm and weighted coexpression network analysis (WGCNA) to construct tumor microenvironment stromal-immune score-based competitive endogenous RNA (ceRNA) networks. Then, the Cox regression model was performed to screen RNAs associated with prostate cancer survival. The differentially expressed gene profile in tumor stroma was significantly enriched in microenvironment functions, like immune response, cancer-related pathways, and cell adhesion-related pathways. Based on these differentially expressed genes, we constructed three ceRNA networks with 152 RNAs associated with the prostate cancer tumor microenvironment. Cox regression analysis screened 31 RNAs as the potential prognostic biomarkers for prostate cancer. The most interesting 8 prognostic biomarkers for prostate cancer included lncRNA LINC01082, miRNA hsa-miR-133a-3p, and genes TTLL12, PTGDS, GAS6, CYP27A1, PKP3, and ZG16B. In this systematic study for ceRNA networks in the tumor environment, we screened out potential biomarkers to predict prognosis for prostate cancer. Our findings might apply a valuable tool to improve prostate cancer clinical management and the new target for mechanism study and therapy.