缺血性脑卒中m^(6)A修饰与免疫微环境相关性分析  

Correlation analysis between m^(6)A modification and immune microenvironment in ischemic stroke

作　　者：梁天 严雁[2] 朱路路 黄小兰 赵直 钟清清 廖芳萍 温政 龙建雄[1] 苏莉[1] LIANG Tian;YAN Yan;ZHU Lulu;HUANG Xiaolan;ZHAO Zhi;ZHONG Qingqing;LIAO Fangping;WEN Zheng;LONG Jianxiong;SU Li(School of Public Health,Guangxi Medical University,Nanning 530021,Guangxi,China;Department of Encephalopathy,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi,China)

机构地区：[1]广西医科大学公共卫生学院,南宁市530021 [2]广西中医药大学第一附属医院脑病科,南宁市530023

出　　处：《内科》2023年第1期1-7,26,共8页Internal Medicine

基　　金：广西自然科学基金项目(2018GXNSFDA050005);国家自然科学基金项目(81874395)。

摘　　要：目的 初步探究N^(6)-甲基腺苷(m^(6)A)调节因子在缺血性脑卒中(IS)免疫微环境中的潜在作用与机制。方法 基于基因表达综合数据库(GEO),应用单样本基因集富集分析(ssGSEA)、一致性聚类分析和基因集富集分析(GSEA)等生物信息学方法综合分析m^(6)A调节因子与IS免疫微环境的相关性。结果 Spearman相关分析结果显示,IGF2BP2 mRNA的表达与CD56亮自然杀伤细胞富集分数的正相关关系最强(rs=0.66),IGF2BP2 mRNA的表达与2型T辅助细胞富集分数的负相关关系最强(rs=-0.64);ELF3 mRNA的表达与TGFb家族成员富集分数的正相关关系最强(rs=0.56),ELAVL1 mRNA的表达与趋化因子富集分数的负相关关系最强(rs=-0.66)(均P<0.05)。一致性聚类分析确定了两种具有不同m^(6)A修饰模式的IS亚型,亚型1中活化B细胞、活化CD4 T细胞、活化CD8 T细胞、效应记忆CD8 T细胞、自然杀伤T细胞和2型T辅助细胞的富集分数均高于亚型2(均P<0.05),而活化树突状细胞、CD56亮自然杀伤细胞和浆细胞样树突状细胞的富集分数均低于亚型2(均P<0.05);亚型1在白细胞介素和TCR信号通路的富集分数均高于亚型2(均P<0.05),而在TGFb家族成员和TNF家族成员的富集分数均低于亚型2(均P<0.05)。GSEA结果表明,亚型2可能与嗅觉转导、紧密连接和白细胞经内皮迁移等信号通路动态相关。结论 m^(6)A修饰与IS免疫微环境存在相关性。Objective To preliminarily investigate the potential role and mechanism of N^(6)-methyladenosine(m^(6)A)regulators in the immune microenvironment of ischemic stroke(IS).Methods Based on the Gene Expression Omnibus(GEO)database,the correlation between m^(6)A regulators and the IS immune microenvironment was comprehensively analyzed by using bioinformatics methods such as single-sample gene set enrichment analysis(ssGSEA),consistency cluster analysis,and gene set enrichment analysis(GSEA).Results The results of Spearman correlation analysis showed that the expression of IGF2BP2 mRNA had the strongest positive correlation with the enrichment score of CD56 bright natural killer cells(r s=0.66),and the expression of IGF2BP2 mRNA had the strongest negative correlation with the enrichment score of type 2 T helper cells(r s=-0.64).The expression of ELF3 mRNA had the strongest positive correlation with the enrichment score of TGFb family members(r s=0.56),and the expression of ELAVL1 mRNA had the strongest negative correlation with the enrichment score of chemokines(r s=-0.66)(all P<0.05).The consistency clustering analysis identified two IS subtypes with different m^(6)A modification patterns,subtype 1 had higher enrichment scores of activated B cells,activated CD4 T cells,activated CD8 T cells,effector memory CD8 T cells,natural killer T cells,type 2 T helper cells,interleukins,and TCR signaling pathway,but lower enrichment scores of activated dendritic cells,CD56 bright natural killer cells,plasmacytoid dendritic cells,TGFb family members,and TNF family members compared with subtype 2(all P<0.05).The results of GSEA indicated that subtype 2 may be dynamically correlated to signaling pathways such as olfactory transduction,tight junction,and leukocyte transendothelial migration.Conclusion There is a correlation between m^(6)A modification and the IS immune microenvironment.

关 键 词：缺血性脑卒中 N^(6)-甲基腺苷 免疫微环境 聚类分析 富集分析 生物信息学 

分 类 号：R743.33[医药卫生—神经病学与精神病学]