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.
Highlights
Bladder cancer (BC) is the 10th most common cancer globally [1] and is characterized by high morbidity and mortality rates [2]
We identified 14,086 long non-coding RNAs (lncRNAs) in the The Cancer Genome Atlas (TCGA) datasets by analyzing the annotated files downloaded from the GENCODE website
To analyze the potential relationship between m6A-related lncRNAs and the tumor microenvironment (TME) of bladder cancer (BC), the level of immunocyte infiltration in cluster 1 and cluster 2 was evaluated, and we found that the infiltration level of naïve CD4 T cells, regulatory T cells (Tregs), memory B cells and plasma cells was relatively high in cluster 1, and that of neutrophils and activated memory CD4 T cells was relatively high in cluster 2 (Figure 4D)
Summary
Bladder cancer (BC) is the 10th most common cancer globally [1] and is characterized by high morbidity and mortality rates [2]. Some advanced urinary assays could detect the early-stage bladder cancer leading to m6A-Related LncRNAs in BC early treatment, the approach to predict the prognosis of bladder cancer and help clinical decision making is lacking and unsatisfied [5, 6]. It is of great significance to predict and differentiate tumors of different subtypes based on tumor heterogeneity to individualize treatment approaches and improve the therapeutic effect while reducing the application of unnecessary treatment. The molecular typing system can better reflect the intrinsic characteristics of BC than traditional pathological typing, it is not viable for clinical application because of its high cost and complexity. The search for new economically viable and effective prediction methods is of great significance for improving the prognosis of BC and realizing individualized treatment
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