Background: To analyze the effect of N6-methyladenosine (m6A) RNA methylation regulators on the immune infiltration and prognosis of bladder cancer (BC). We explored the related signaling pathways and prognosis-related genes to provide candidate targets for the treatment and prognostic evaluation of BC.
Methods: After downloading BC data from The Cancer Genome Atlas (TCGA) database, the expressions of m6A-related genes were obtained. We then performed correlation and sample cluster analysis of the m6A methylation regulator genes as well as difference comparison and survival analysis for the clustered patients using R software. Gene set enrichment analysis (GSEA) was carried out on cluster-grouped samples. Finally, the prognosis-related genes of BC among the m6A methylation regulators were screened.
Results: Genomic alterations in the m6A regulators were linked to a poor BC prognosis. HNRNPA2B1, HNRNPC, IGF2BP2, RBM15, YTHDF1, and YTHDF2 were found to be associated with advanced clinical stages of BC. Furthermore, the current study revealed that the levels of the m6A regulators were related to the expression levels and immune infiltration levels of immune regulators [immunosuppressive factors, immunostimulators, and major histocompatibility complex (MHC) molecules] in BC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses suggested that in addition to the relevant immune responses, m6A regulators were involved in the poor prognosis of BC via their participation in blood vessels through regulatory RNA binding, telomeric DNA binding, microRNA (miRNA) binding, negative regulation of messenger RNA (mRNA) processing, negative regulation of DNA biosynthesis, branches of morphogenesis, positive regulation of the Notch receptor target gene transcription, etc.
Conclusions: The expression of m6A RNA methylation regulators is closely linked to immune infiltration and prognosis in BC. Thus, it can be utilized as a potential molecular target for the treatment and prognostic assessment of BC.
Keywords: Bioinformatics; N6-methyladenosine regulating factor (m6A regulating factor); bladder cancer (BC); immune infiltration; prognosis.
2022 Annals of Translational Medicine. All rights reserved.