Comprehensive analysis of the functions and prognostic significance of RNA-binding proteins in bladder urothelial carcinoma

Abstract Background Alterations in RNA-binding proteins (RBPs) are reported in various cancer types; however, the role of RBPs in bladder urothelial cancer (BLCA) remains unknown. This study aimed to systematically examine the function and prognostic significance of RBPs in bladder cancer using bioinformatics analyses. Methods RNA sequencing and clinical data for BLCA were downloaded from The Cancer Genome Atlas (TCGA) database, and differentially expressed RBPs (DERBPs) between normal and cancer tissues were identified. Protein-protein interaction (PPI) network of DERBPs was established, and enrichment analysis and visualizations were performed. A total of 404 patients with BLCA from TCGA database were randomly divided into training and testing groups. A prognostic model was constructed using the data from training group, and validated in the testing group. Receiver operating characteristic (ROC) curve and survival analysis were performed to explore the prognostic value of the model. A nomogram was established to predict survival in bladder cancer patients. Finally, the verification of prognosis-related hub RBP survival analysis were performed. Results A total of 388 DERBPs were identified, including 219 upregulated and 169 downregulated RBPs. All RBPs were screened for prognostic model establishment and 9 RBPs (TRIM71, YTHDC1, DARS2, XPOT, ZNF106, FTO, IPO7, EFTUD2, and CTU1) were regarded as prognosis-related hub RBPs in BLCA. Further analysis revealed worse overall survival (OS) in the high-risk cohort compared to the model-based low-risk cohort. The area under the ROC curve was 0.752 in the training group and 0.701 in the testing group, which confirms the good prediction ability. A nomogram was established according to nine prognosis-related RBPs, which showed well predicting ability for BLCA. BLCA patients with high DARS2, XPOT, ZNF106, FTO, and IPO7 expression (on the contrary, low YTHDC1 and CTU1 expression) were correlated to poor overall survival. Conclusions The prognosis-related hub RBPs may be involved in oncogenesis, development, and metastasis of BLCA. Our results will be of great significance in revealing the pathogenesis of BLCA, and developing new therapeutic targets and prognostic molecular markers.