Identification of the Six-RNA-Binding Protein Signature for Prognosis Prediction in Bladder Cancer.

Yucai Wu,Cuijian Zhang,Anbang He,Zhengjun Kang,Yi Liu,Yanqing Gong,Shiming He,Xuesong Li,Bao Guan,Liqun Zhou

doi:10.3389/fgene.2020.00992

Abstract

RNA-binding proteins (RBPs) are a kind of gene regulatory factor that presents a significant biological effect in the initiation and development of various tumors, including bladder cancer (BLCA). However, the RBP-based prognosis signature for BLCA has not been investigated. In this study, we attempted to develop an RBP-based classifier to predict overall survival (OS) for BLCA based on transcriptome analysis. We extracted data of BLCA patients from The Cancer Genome Atlas database (TCGA) and UCSC Xena. Finally, a total of 398 cases without missing clinical data were enrolled and six RBPs (FLNA, HSPG2, AHNAK, FASTKD3, POU5F1, and PCSK9) associated with OS of BLCA were identified through univariate and multivariate Cox regression analysis. Online analyses and immunohistochemistry validated the prognostic value and expression of six RBPs. Risk scores were calculated to divide patients into high-risk and low-risk level, and patients in the high-risk group tended to have a poor prognosis. In addition, the receiver operating characteristic (ROC) curve analysis was performed to assess the prognostic value of RBPs, and the area under the curve (AUC) values were 0.711 and 0.706, respectively, in the training set and validating set. The findings were further validated in an external validation set. Subsequently, the 6-RBP-based signature and pathological stage were used to construct the nomogram to predict the 3- and 5-years OS of BLCA patients. Also, this 6-RBP-based signature was highly related to recurrence-free survival of BLCA. Weighted co-expression network analysis (WGCNA) combined with functional enrichment analysis contributed to study the potential pathways of six RBPs, including keratinocyte differentiation, RHO GTPases activate PNKs, epithelial tube morphogenesis, establishment or maintenance of cell polarity, and so on. In summary, the 6-RBP-based signature holds the potentiality to serve as a novel prognostic predictor of OS for BLCA.

Highlights

Bladder cancer (BLCA) is the 10th most prevalent cancer and the most frequently diagnosed malignancy of the urinary system all over the world (Bray et al, 2018)
A total of 1348 genes coding known or predicted RNA-binding proteins (RBPs) were matched with the 4456 differentially expressed genes (DEGs) and 109 RBPs remained
Clinical characters of BLCA patients were downloaded from the UCSC database, and these cases were randomly divided into training set (n = 265) and validating set (n = 133) at a 2:1 ratio

Summary

Introduction

Bladder cancer (BLCA) is the 10th most prevalent cancer and the most frequently diagnosed malignancy of the urinary system all over the world (Bray et al, 2018). Non-metastatic BLCA is separated into non-muscleinvasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) and approximately 70% of BLCA patients belong to NMIBC when initially diagnosed (Dobruch et al, 2016). MIBC patients have a more favorable prognosis than those with locally advanced and metastatic BLCA due to the limited effects of surgery on advanced BLCA. BLCA is the cancer with high recurrence and about half of patients after radical surgery relapse and present with metastases (Alfred Witjes et al, 2017). No specific symptoms appeared in the early stage of tumor, which makes it urgent to develop novel biomarkers to predict the survival of BLCA

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