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.

Serum multi-cytokines screening identifies TRAIL and IL-10 as probable new biomarkers for prostate health index diagnostic utility adjustment in grey zone aggressive prostate cancer detection: A single-center data in China

“…Consistent with the results of recent studies the risk factor immune response was found to be related to aggressive prostate cancer progression and resistance to drug treatment ( 24 – 26 ), which may further direct urologists for grey zone aggressive prostate cancer early risk stratification. Functioning as one of the tumor necrosis factor ligand family, TRAIL has been reported to induce apoptosis in tumor cells preferentially.…”

Bioinformatics study of PCDHB6 as a prognostic marker for gastric cancer

“…The bacterium mainly causes gastric cancer by adhering to and in ltrating the epithelial cells of the gastric mucosa and adding value [22]. Recent studies have reported that differentially expressed genes in the tumor microenvironment induce migration and invasion of prostate cancer by participating in the regulation of cell adhesion-related pathways [23]. Consistent with our ndings, it is hypothesized that PCDHB6 may be involved in certain pathways that exacerbate gastric carcinogenesis, and the speci c regulatory processes need to be further investigated.…”

hsa‐mir‐133a‐2 promotes the proliferation and invasion of cervical cancer cells by targeting the LAMB3‐mediated PI3K/ATK pathway

“…hsa‐mir‐133a‐2 is located on chromosome number 20. Numerous studies have demonstrated that it is abnormally expressed in solid tumors such as colorectal cancer, breast cancer and prostate cancer, and that it is closely associated to tumor patient prognosis 9–11 . In addition, hsa‐mir‐133a‐2 was also found to be involved in the regulation of tumor cell proliferation, migration, invasion, and drug resistance, indicating its significant potential as a tumor therapeutic target 12 .…”