Data_Sheet_7_N6-methyladenosine modulation classes and immune microenvironment regulation in ischemic stroke.XLSX
收藏frontiersin.figshare.com2023-06-21 更新2025-03-22 收录
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N6-methyladenosine (m6A) modifications play an important role in the differentiation and regulation of immune cells. However, research on m6A in ischemic stroke (IS) is still in its infancy, and their role of the immune microenvironment remains unknown. In this study, we systematically assessed the modification classes of m6A regulators in IS based on the GEO database (GSE16561 and GSE22255). We found that in IS patients, IGF2BP2, IGF2BP1, and YTHDF2 expression was significantly upregulated, and ELAVL1, LRPPRC, METTL3, ALKBH5, CBLL1, and METTL14 expression was significantly downregulated. Seven IS-related genes (ELAVL1, IGF2BP2, LRPPRC, YTHDF2, ALKBH5, METTL14, and YTHDC1) were finally screened by logistic and least absolute shrinkage and selection operator (LASSO) regressions, and the AUC of the riskScore was 0.942, which was a good classification. For immune infiltration, there were highly significant differences in memory B cells, CD8 T cells, monocytes, activated dendritic cells, and mast cells between IS and normal samples. The IS samples were grouped into three classes by consistent clustering, and 15 m6A genes were differentially expressed in the different classes. Multiple infiltrating immune cells, immune-associated genes, and HLA-associated genes differed significantly across m6A modification classes, indicating the diversity and complexity of m6A modifications in the immune microenvironment of IS. Finally, 487 genes associated with the m6A modification class were identified, and 227 potential drugs were found. Our findings demonstrated that m6A modification plays a crucial role in the immune regulation of IS.
N6-甲基腺苷(m6A)修饰在免疫细胞的分化和调控中扮演着至关重要的角色。然而,关于缺血性卒中(IS)中m6A的研究尚处于起步阶段,其在免疫微环境中的功能尚不明确。在本研究中,我们基于GEO数据库(GSE16561和GSE22255)对IS中m6A调节因子的修饰类型进行了系统评估。我们发现,在IS患者中,IGF2BP2、IGF2BP1和YTHDF2的表达显著上调,而ELAVL1、LRPPRC、METTL3、ALKBH5、CBLL1和METTL14的表达则显著下调。通过逻辑回归和最小绝对收缩和选择算子(LASSO)回归,最终筛选出七个与IS相关的基因(ELAVL1、IGF2BP2、LRPPRC、YTHDF2、ALKBH5、METTL14和YTHDC1),其风险评分的AUC值为0.942,具有良好的分类效果。在免疫浸润方面,IS与正常样本之间在记忆B细胞、CD8 T细胞、单核细胞、活化树突状细胞和肥大细胞之间存在高度显著的差异。通过一致性聚类,将IS样本分为三个类别,并在不同类别中检测到15个差异表达的m6A基因。多重浸润的免疫细胞、免疫相关基因和HLA相关基因在m6A修饰类别之间存在显著差异,这表明在IS的免疫微环境中,m6A修饰的多样性和复杂性。最终,识别出与m6A修饰类别相关的487个基因,并发现了227种潜在药物。我们的研究结果表明,m6A修饰在IS的免疫调节中发挥着至关重要的作用。
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