Insights From m6A RNA Methylation: Biomarkers for Diagnosis of Acute Myocardial Infarction

Wenjun Fan,1,2 Wenbin Zhao,1,2 Renjie Hu,1,2 Chen Wei,3 Lixian Sun,3 Tong Hou,1,2 Ran Li,1,2 Qinghua Sun,1,2 Cuiqing Liu1,2 1School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, 310053, People’s Republic of China; 3Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of ChinaCorrespondence: Cuiqing Liu, School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Tel +86 571 86611320, Email [email protected]: Acute myocardial infarction (AMI) is a major contributor to death. The purpose of this study is to explore circulating biomarkers for AMI diagnosis from the perspectives of immunological microenvironment and N6-methyladenosine (m6A) RNA methylation regulation.Patients and Methods: The GSE59867 dataset was used to download platform and probe data for conducting differential analysis of m6A regulators. A diagnostic nomogram was created utilizing the random-forest method and evaluated for predictive power. m6A-related gene patterns were identified, and their immune microenvironment characteristics were analyzed. Peripheral blood samples were obtained for validation in patient-based investigations using RT-qPCR. The association between m6A regulators and clinical parameters was examined via Spearman correlation analysis.Results: With a predictive nomogram model developed using key m6A regulators, two distinct m6A subtypes were identified, showing significant variations in infiltrating immunocyte abundance. In confirmation of the model prediction, examination of patient blood identified METTL3, WTAP, RBM15, ALKBH5, FTO, and FMR1 as novel circulating biomarkers for AMI diagnosis. METTL3 and FTO were identified as promising biomarkers for AMI given that they showed a positive correlation with left ventricular ejection fraction.Conclusion: The study identified six m6A regulators as circulating biomarkers for AMI diagnosis and suggested a potential role for m6A-mediated immune cell infiltration in the pathogenesis of AMI.Keywords: acute myocardial infarction, immune cell infiltration, N6-methyladenosine, diagnosis, biomarker