Molecular network-based identification of competing endogenous RNAs and mRNA signatures that predict survival in prostate cancer.

ABSTRACT

BACKGROUND: The aim of the study is described the regulatory mechanisms and prognostic values of differentially expressed RNAs in prostate cancer and construct an mRNA signature that predicts survival. METHODS: The RNA profiles of 499 prostate cancer tissues and 52 non-prostate cancer tissues from TCGA were analyzed. The differential expression of RNAs was examined using the edgeR package. Survival was analyzed by Kaplan-Meier method. microRNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) networks from the miRcode database were constructed, based on the differentially expressed RNAs between non-prostate and prostate cancer tissues. RESULTS: A total of 773 lncRNAs, 1417 mRNAs, and 58 miRNAs were differentially expressed between non-prostate and prostate cancer samples. The newly constructed ceRNA network comprised 63 prostate cancer-specific lncRNAs, 13 miRNAs, and 18 mRNAs. Three of 63 differentially expressed lncRNAs and 1 of 18 differentially expressed mRNAs were significantly associated with overall survival in prostate cancer (P value < 0.05). After the univariate and multivariate Cox regression analyses, 4 mRNAs (HOXB5, GPC2, PGA5, and AMBN) were screened and used to establish a predictive model for the overall survival of patients. Our ROC curve analysis revealed that the 4-mRNA signature performed well. CONCLUSION: These ceRNAs may play a critical role in the progression and metastasis of prostate cancer and are thus candidate therapeutic targets and potential prognostic biomarkers. A novel model that incorporated these candidates was established and might provide more powerful prognostic information in predicting survival in prostate cancer.