Comprehensive Analysis of N6-Methylandenosine-Related Long Non-Coding RNAs Signature in Prognosis and Tumor Microenvironment of Bladder Cancer

Abstract

To investigate the role of N6-methyladenosine (m6A)- related long non-coding RNAs (lncRNAs) in bladder cancer (BC). 50 m6A-related lncRNAs were screened out and were correlated with prognosis from BC samples in The Cancer Genome Atlas (TCGA). The lncRNAs were subdivided into cluster 1 and cluster 2 with consensus cluster analysis, and it was found that lncRNAs in cluster 2 were associated with poor prognosis and increased PD-L1 expression. Gene set enrichment analysis (GSEA) revealed tumor-related pathways in cluster 2. Through least absolute shrinkage and selection operator (LASSO) Cox regression analysis, univariate and multivariate Cox regression, and ROC analyses, 14 prognostic lncRNAs were selected and used to construct the m6A-related lncRNA prognostic signature (m6A-LPS), furthermore, that m6A-LPS was as a valuable independent prognostic factor. Interestingly, the m6A-LPS risk score was positively correlated with the immune score, PD-L1 expression, and the infiltration of immune cell subtypes in BC. SNHG16, a member of the high-risk group based on m6A-LPS, was highly expressed in BC tissues and cell lines and interfered with siRNA resulted in suppressed proliferation, migration, and invasion in vitro. Our study illustrates the role of m6A-related lncRNAs in BC. The m6A-LPS may be an important regulatory target of the tumor microenvironment (TME) in BC.