Comprehensive analysis of N6-methyladenosine regulators with the tumor immune landscape and correlation between the insulin-like growth factor 2 mRNA-binding protein 3 and programmed death ligand 1 in bladder cancer

Background N.sup.6-methyladenosine (m.sup.6A) is one of the most abundant post-transcriptional modifications of RNA. However, there is limited information about the potential roles of m.sup.6A regulators in tumor immunity. Therefore, in this study, we aimed to testify the functions of m.sup.6A regulators in bladder cancer as well as their association with the tumor immune landscape. Methods We reported the variation and expression levels of m6A regulators in the TCGA database and GTEx database of bladder cancer. Clusters, risk score patterns, and nomograms were constructed to evaluate the function and prognostic value of m.sup.6A regulators. Furthermore, we constructed nomogram to evaluate the prognosis of the individual patients. The correlation between insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and programmed cell death ligand 1 (PD-L1) was evaluated both in vitro and in vivo. Results We found that the tumor grade and DNA damage pathways were strongly correlated with distinct clusters. Furthermore, two risk score groups with six m.sup.6A regulators were identified using the least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analysis, which could be regarded as independent prognostic markers in patients with bladder cancer. The risk score pattern was linked to the tumor immune landscape, indicating a correlation between immune checkpoints and m.sup.6A regulators. Moreover, an m.sup.6A regulator, IGF2BP3, was found to be highly expressed in the tumor samples, regulating both the total and membrane-bound PD-L1 expression levels. Conclusions The results of this study revealed that the m.sup.6A clusters and patterns play crucial roles in the regulation of tumor immunity, which may be used to develop comprehensive treatment strategies for the management of bladder cancer. Keywords: m.sup.6A, Immune landscape, Bladder cancer, IGF2BP3, PD-L1