Exploring the Interplay of m6A Regulators in Renal Cell Carcinoma: Molecular Insights and clinical implications

Abstract

BackgroundThe m6A modification of N6-methyladenosine (m6A) modification regulates gene expression and functioning by affecting RNA splicing, stability, translocation, and translation. ObjectiveThis study used comprehensive bioinformatics analysis to elucidate the mechanisms by which m6A regulators function in kidney renal clear cell carcinoma (KIRC) and their interrelationships. MethodsThe KIRC data extracted from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases was used in this study. LASSO Cox regression, protein–protein interaction analysis, univariate Cox regression, and a predictive risk model. Cox regression, Kaplan–Meier analysis, consensus clustering, CIBERSORT, gene set enrichment analysis (GSEA), ESTIMATE, immune cell infiltration, and prognostic factors were investigated in KIRC utilizing computational methods. ResultsThe results of integrated analysis showed that KIRC has unique and complex gene patterns associated with m6A and is linked to different gene patterns. These patterns included an 11.68-fold change in insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3), a 3.35-fold change in ELAV-like RNA binding protein 2 (ELAVL2), a 2.34-fold change in fat mass- and obesity-associated protein (FTO), a 2.52-fold change in ELAVL4, and a 2.15-fold change in ELAVL3. By contrast, there was downregulation of IGF2BP2, zinc finger CCCH-type containing 14 (ZC3H14), and alpha-ketoglutarate-dependent dioxygenase (ALKBH6), with fold changes of 0.44, 0.66, and 0.68, respectively. Minor modifications ranging from 1 to 1.28 were seen in other m6A regulators. ConclusionThis study showed that m6A alteration affects KIRC tumor immunity. Moreover, m6A regulators such as IGF2BP3 have therapeutic and diagnostic potential, which could improve patient outcomes by personalized immunotherapy.