Abstract
Abnormal m6A methylation plays a significant role in cancer progression. Increasingly, researchers have focused on developing lncRNA signatures to evaluate the prognosis of cancer patients. The specific function of m6A-related lncRNAs in the prognosis of bladder cancer patients and the immune microenvironment of bladder cancer remains elusive. Herein, we performed a comprehensive analysis of m6A-related lncRNA prognostic values and their association with the immune microenvironment in bladder cancer using the TCGA dataset. A total of 9 m6A-related lncRNAs were dramatically correlated with overall survival outcomes in bladder cancer. Two molecular subtypes (cluster 1 and cluster 2) were identified by consensus clustering for 9 m6A-related prognostic lncRNAs. Cluster 1 was significantly correlated with poor prognosis, advanced clinical stage, higher PD-L1 expression, a higher ESTIMATEScore and immuneScore, and distinct immune cell infiltration. GSEA revealed the enrichment of apoptosis and the JAK-STAT signaling pathway in cluster 2. A prognostic risk score was constructed using 9 m6A-related prognostic lncRNAs, which functioned as an independent prognostic factor for bladder cancer. Moreover, bladder cancer patients in the low-risk score group had a higher pN stage, pT stage, and clinical stage and a lower tumor grade and immuneScore. The risk score was correlated with the infiltration levels of certain immune cells, including B cells, plasma cells, follicular helper T cells, regulatory T cells, resting NK cells, neutrophils, M0 macrophages, M1 macrophages, and M2 macrophages. Collectively, our study elucidated the important role of m6A-related lncRNAs in the prognosis of bladder cancer patients and in the bladder cancer immune microenvironment. The results suggest that the components of the m6A-related prognostic lncRNA signature might serve as a crucial mediator of the immune microenvironment in bladder cancer, representing promising therapeutic targets for improving immunotherapeutic efficacy.
Highlights
Bladder cancer (BC) is one of the most frequent urinary malignancies in China and has a high incidence rate [1]
Based on the Long noncoding RNAs (lncRNAs) annotation file in GENCODE, we identified 14087 lncRNAs in the TCGA bladder cancer dataset
Based on the prognostic value of these m6A-related lncRNAs, a univariate Cox regression analysis was performed to identify m6A-related prognostic lncRNAs with a p value of 0.0001. e data revealed that 9 m6A-related lncRNAs were markedly associated with overall survival (OS) in bladder cancer patients (Figure 2(b) and Table 2)
Summary
Bladder cancer (BC) is one of the most frequent urinary malignancies in China and has a high incidence rate [1]. Transitional cell carcinoma ranks approximately 90% of bladder cancer. Most of the BCs are nonmuscle invasive (MI) BCs, which readily relapse and develop into muscle invasive bladder cancers [2]. 30% of bladder cancers are MIBCs, whose gold standard for their treatment is radical cystectomy and pelvic lymph node dissection [3]. Several clinical features and molecular biomarkers have been applied for the prognosis of bladder cancer patients, these approaches are all limited to some extent. Us, it is necessary to construct a new predictive model and identify new prognostic markers for bladder cancer. Abnormal m6A methylation is involved in the progression of cancer by regulating various biological
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