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

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.

A New RBPs-Related Signature Predicts the Prognosis of Colon Adenocarcinoma Patients

“…RBPs are a group of genes that regulate the growth, development and survival of cancer cells, and are closely related to cancer progression ( 30 , 31 ). For instance, IGF2BP3 may contributes to lung tumorigenesis by regulating the alternative splicing of PKM ( 32 ), HuR promotes the progression of head and neck squamous cell carcinoma and bladder cancer ( 33 , 34 ).…”

Identification of the Functions and Prognostic Values of RNA Binding Proteins in Bladder Cancer

“…To determine whether our RBPs-related prognostic model was superior to other prognostic models, we compared our model with 6 RBPs (Wu et al, 2020) model and 9 RBPs model (Guo et al, 2020). Relevant prognostic genes were obtained from the corresponding literature, and survival curves and ROC curves were constructed based on the entire TCGA cohort, respectively.…”

Identification of a chromatin regulator signature and potential candidate drugs for bladder cancer

“…Several diagnostic and prognostic biomarkers, including mRNAs, miRNAs, lncRNAs, and circRNAs, have been identified for cancers [ 29 – 32 ]. Risk models with high prognostic accuracy were identified as potential prognostic biomarkers based on RNA-binding proteins in many cancer types [ 33 – 35 ]. Prognostic indicators based on long non-coding RNAs have been reported in several pieces of researches such as immune-related lncRNAs [ 36 , 37 ] and autophagy-related lncRNAs [ 38 , 39 ], which also showed well performance in predicting the overall survival of cancer patients.…”