m6A-Related lncRNA to Develop Prognostic Signature and Predict the Immune Landscape in Bladder Cancer

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.

Dynamic Changes in Myofibroblasts Affect the Carcinogenesis and Prognosis of Bladder Cancer Associated With Tumor Microenvironment Remodeling

“…Predictive models based on bioinformatics analysis are widely available in the field of BLCA research, and many of them show high predictive accuracy ( Abudurexiti et al, 2019 ; Li Z. et al, 2021 ; Du et al, 2021 ). However, there are still fewer diagnostic models for predicting the carcinogenesis of BLCA.…”

Application of m6A and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma

“…ese processes help to protect tumor cells from clearance, inhibit cell death, and promote proliferation to further aid tumor cell migration and metastasis. Most of the current studies have focused on immunomodulation of tumors [28], focusing on addressing the sustained suppression of adaptive immune responses by TME [29]. Encouragingly, previous studies have demonstrated a strong association between m 6 A methylation and tumor immunotherapy; for example, studies have reported a broad regulatory mechanism of m 6 A on the tumor microenvironment in gastric cancer [25].…”

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

“…There is no doubt that m6A methylation has significant potential for the development of new human cancer therapies. Additionally, bioinformatics show that m6A participates in BC via multiple biological processes: m6A regulators contribute to malignant progression and impact on prognoses ( Chen et al, 2019d ), m6A contributes to tumor microenvironments ( Zhu et al, 2021b ), and m6A regulates lncRNA in BC carcinogenesis ( Li et al, 2021f ). Moreover, bioinformatics tools can be used to study associations between m6A and BC.…”