Objective: To develop a prognostic signature for patients with bladder cancer (BC). Methods: We identified differentially expressed miRNAs between normal bladder tissue and bladder cancer in the TCGA-BCLA dataset and evaluated prognostic values of these miRNAs. Then, a 21-miRNA signature was constructed based on the results of Cox proportional hazards regression model. Furthermore, functional enrichment analyses were conducted to explore the potential effects of the target genes of these 21 miRNAs. Results: Seventy six differentially expressed miRNAs were identified, among which 21 miRNAs including hsa-let-7c, mir-143, mir-944, mir-192, mir-590, mir-490, mir-141, mir-93, mir-1-2, mir-200c, mir-133a-1, mir-1-1, mir-133b, mir-20a, mir-185, mir-19a, mir-19b-2, mir-19b-1, mir-17, mir-15a, and mir-133a-2 were demonstrated to be significantly correlated with the overall survival (OS) of bladder cancer patients using Kaplan-Meier survival analysis and Log-rank test. The results of Chi-square test and multivariable logistic regression analysis showed that the 21-miRNA signature was significantly associated with the diagnosis type and T stage of bladder cancer. Univariate and multivariable survival analyses indicated that the 21-miRNA signature was an independent factor in predicting the overall survival of patients with bladder cancer. The results of functional enrichment analysis suggested that the target genes of these 21 miRNAs were mostly enriched in critical cancer-related biological processes and pathways, and the PPI network suggested that 60 targeted genes interacted with a minimum of 30 genes were at the hub of the whole network. In addition, we performed a multivariate nomogram and decision curve analysis (DCA) to evaluate the clinical application of 21-microRNA signature. Conclusion: We introduced a 21-miRNA signature which was associated the prognosis of patients of bladder cancer, and inspirational ideas for the future basic and clinical exploration.

Frontiers in oncology. 2019 Aug 07*** epublish ***

Xiao-Hong Yin, Ying-Hui Jin, Yue Cao, York Wong, Hong Weng, Chao Sun, Jun-Hao Deng, Xian-Tao Zeng

Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China., School and Hospital of Stomatology, Wuhan University, Wuhan, China., Department of Orthopedic, Xinqiao Hospital of Army Medical University, Chongqing, China., Department of Orthopedic, Chinese PLA General Hospital, Beijing, China.