m6A regulator-mediated RNA methylation modification patterns are involved in immune microenvironment regulation of ischaemic cardiomyopathy

Abstract

Abstract The RNA N6-methyladenosine (m6A) modification pattern plays a key role in immunity. However, the role of m6A in the regulation of the immune microenvironment in ischaemic cardiomyopathy (ICM) remains unclear. This study first identified differential m6A regulators between ICM and normal samples and then systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 118 ICM samples. Specifically, the effect of m6A modification on the characteristics of the immune microenvironment in ICM was explored, including infiltrating immune cells, human leukocyte antigen (HLA) genes and HALLMARKS pathways. A total of seven key m6A regulators were identified by the random forest classifier. Compared with healthy samples, one m6A regulator, WTAP, was downregulated, and a total of 6 m6A regulators, ZCH3H13, YTHDC1, FMR1, FTO, RBM15 and YTHDF3, were upregulated in ICM samples. A diagnostic nomogram based on these seven key m6A regulators can effectively distinguish patients with ICM from healthy subjects. Two distinct RNA modification patterns (m6A cluster-A and -B) mediated by 7 key m6A regulators were identified. The cell infiltration patterns and the expression of 16 HLA genes were significantly different between the m6A cluster-A and m6A cluster-B groups. The m6A regulators YTHDF3, FMR1, ZC3H13 and RBM15 were significantly correlated with several immune cells. Moreover, differential HALLMARKS signalling pathways between the m6A cluster-A and m6A cluster-B groups were also identified. The current research suggests that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of ICM. Seven key m6A regulators, WTAP, ZCH3H13, YTHDC1, FMR1, FTO, RBM15 and YTHDF3, may be novel biomarkers for the accurate diagnosis of ICM. Immunotyping of patients with ICM will help to develop more accurate immunotherapy strategies for those with a significant immune response.