Cardiology Department, Hunan Provincial People’s Hospital, Furong, Changsha 410000, Hunan, China.
Clinical Research Center for Heart Failure in Hunan Province, Furong, Changsha 410000, Hunan, China.
Aging (Albany NY). 2023 Feb 20;15(5):1371-1393. doi: 10.18632/aging.204537.
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 and 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 and 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 and genes may be novel biomarkers for the accurate diagnosis and immunotherapy of AF.
m6A 在心房颤动 (AF) 免疫微环境调控中的作用尚不清楚。本研究系统评估了 62 例 AF 样本中差异 m6A 调节因子介导的 RNA 修饰模式,鉴定了 AF 中免疫细胞浸润的模式,并鉴定了几个与 AF 相关的免疫相关基因。通过随机森林分类器鉴定了健康受试者和 AF 患者之间的 6 个关键差异 m6A 调节因子。基于 6 个关键 m6A 调节剂的表达,在 AF 样本中确定了三种不同的 RNA 修饰模式(m6A 簇-A、-B 和 -C)。鉴定了正常和 AF 样本以及具有三种不同 m6A 修饰模式的样本之间差异浸润免疫细胞和 HALLMARKS 信号通路。通过加权基因共表达网络分析 (WGCNA) 结合两种机器学习方法,共鉴定出 16 个重叠关键基因。和 基因的表达水平在对照和 AF 患者样本之间以及具有不同 m6A 修饰模式的样本之间存在差异。RT-qPCR 还证明与对照组参与者相比,AF 患者中 基因的表达显著增加。这些结果表明,m6A 修饰在 AF 免疫微环境的复杂性和多样性中起关键作用。对 AF 患者进行免疫分型将有助于为具有显著免疫反应的患者开发更精确的免疫治疗策略。和 基因可能是 AF 准确诊断和免疫治疗的新的生物标志物。
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