Research Paper Volume 15, Issue 5 pp 1371—1393
Identification of m6A regulator-mediated RNA methylation modification patterns and key immune-related genes involved in atrial fibrillation
- 1 Cardiology Department, Hunan Provincial People’s Hospital, Furong, Changsha 410000, Hunan, China
- 2 Clinical Research Center for Heart Failure in Hunan Province, Furong, Changsha 410000, Hunan, China
- 3 Institute of Cardiovascular Epidemiology, Hunan Provincial People’s Hospital, Furong, Changsha 410000, Hunan, China
- 4 The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Furong, Changsha 410000, Hunan, China
Received: November 28, 2022 Accepted: February 11, 2023 Published: February 20, 2023
https://doi.org/10.18632/aging.204537How to Cite
Copyright: © 2023 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The role of m6A in the regulation of the immune microenvironment in atrial fibrillation (AF) remains unclear. This study systematically evaluated the RNA modification patterns mediated by differential m6A regulators in 62 AF samples, identified the pattern of immune cell infiltration in AF and identified several immune-related genes associated with AF. A total of six key differential m6A regulators between healthy subjects and AF patients were identified by the random forest classifier. Three distinct RNA modification patterns (m6A cluster-A, -B and -C) among AF samples were identified based on the expression of 6 key m6A regulators. Differential infiltrating immune cells and HALLMARKS signaling pathways between normal and AF samples as well as among samples with three distinct m6A modification patterns were identified. A total of 16 overlapping key genes were identified by weighted gene coexpression network analysis (WGCNA) combined with two machine learning methods. The expression levels of the NCF2 and HCST genes were different between controls and AF patient samples as well as among samples with the distinct m6A modification patterns. RT-qPCR also proved that the expression of NCF2 and HCST was significantly increased in AF patients compared with control participants. These results suggested that m6A modification plays a key role in the complexity and diversity of the immune microenvironment of AF. Immunotyping of patients with AF will help to develop more accurate immunotherapy strategies for those with a significant immune response. The NCF2 and HCST genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.
Abbreviations
m6A: RNA N6-methyladenosine; AF: atrial fibrillation; WGCNA: weighted gene co-expression network analysis; Tregs: regulatory T cells; SR: sinus rhythm; PCA: principal component analysis; m5C: 5-methylcytosine; m1A: N1-methyladenosine; ssGSEA: single-sample gene-set enrichment analysis; GSVA: gene set variation analysis; DCA: decision curve analysis; ROC: receiver operating characteristic; MDSC: myeloid-derived suppressor cell; GEO: Gene Expression Omnibus; LASSO: Least Absolute Shrinkage and Selector Operation; SVM-RFE: SVM-RFE; NCF2: neutrophil cytosolic factor 2; LAPTM5: lysosomal protein transmembrane 5; HCST: hematopoietic cell signal transducer; HCLS1: hematopoietic cell-specific Lyn substrate 1; CXCL12: C-X-C motif chemokine ligand 12; CORO1A: coronin 1A; C1QC: complement C1q C chain; AMICA1: junction adhesion molecule like; ANOVA: analysis of variance; SLE: systemic lupus erythematosus; HCST: hematopoietic cell signal transducer; ccRCC: clear cell renal cell carcinoma; KIRC: kidney renal clear cell carcinoma; KEGG: Kyoto Encyclopedia of Genes and Genomes; GO: gene ontology; MMP: matrix metalloproteinase; Treg: regulatory T; Th17: type-17 T helper; IL: interleukin; MHC: major histocompatibility complex.