Comprehensive Characterization of m6A Regulators-Mediated Methylation Modification Patterns and Tumor Microenvironment Signature in Breast Cancer

Abstract BackgroundRecent studies have identified the epigenetic regulation in the tumor immune microenvironment (TME). Nonetheless, RNA N6-methyladenosine (m6A) modification mediated TME cell infiltration in breast cancer is still unknown. MethodsHerein, we systematically explored m6A modification TME infiltration characteristics of 2249 breast cancer patients and comprehensively correlated the m6 A modification patterns with tumor immune landscape. The m6Ascore was established using principal component analysis. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the m6Ascore.ResultsThree m6A modification clusters were identified. The TME cell infiltration characteristics under m6A clusters were consistent with the tumor immune phenotypes (-excluded, -inflamed and -desert). The assessment of m6A modification clusters was able to estimate tumor stages, stromal activity (angiogenesis, CD8+ T effector and EMT), clinical prognosis and genomic mutation. The genetic alternation mediated by m6Ascore was also associated with enhanced response to targeted therapy and immunotherapy. ConclusionThis study demonstrated that m6A regulator-mediated methylation modification plays an important role in TME modulation. Thus, comprehensive evaluation of m6A modification patterns may enhances our understanding of TME modulation and presents a new approach toward targeted therapy and immunotherapeutic strategies for breast patients.