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.

Despite aggressive treatment approaches, muscle-invasive bladder urothelial carcinoma (MIBC) patients still have a 50% chance of developing general incurable metastases. Therefore, there is an urgent need for candidate markers to enhance diagnosis and generate effective treatments for this disease. We evaluated four mRNA microarray datasets to find differences between non-MIBC (NMIBC) and MIBC tissues. Through a gene expression profile analysis via the Gene Expression Omnibus database, we identified 56 differentially expressed genes (DEGs). Enrichment analysis of gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome pathways revealed the interactions between these DEGs. Next, we established a protein-protein interaction network to determine the interrelationship between the DEGs and selected 10 hub genes accordingly. Bladder urothelial carcinoma (BLCA) patients with COL1A2, COL5A1, and COL5A2 alterations showed poor disease-free survival rates, while BLCA patients with COL1A1 and LUM alterations showed poor overall survival rates. Oncomine analysis of MIBC versus NMIBC tissues showed that COL1A1, COL5A2, COL1A2, and COL3A1 were consistently among the top 20 overexpressed genes in different studies. Using the TCGAportal, we noted that the high expression of each of the four genes led to shorter BLCA patient overall survival. It was evident that BLCA patients with an elevated high combined gene expression had significantly shorter overall survival and relapse-free survival than those with low combined gene expression using PROGgeneV2. Using Gene Expression Profiling Interactive Analysis, we noted that COL1A1, COL1A2, COL3A1, and COL5A2 were positively correlated with each other in BLCA. These genes are considered as clinically relevant genes, suggesting that they may play an important role in the carcinogenesis, development, invasion, and metastasis of MIBC. However, considering we adopted a bioinformatic approach, more research is crucial to confirm our results. Nonetheless, our findings may have important prospective clinical implementations.

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