急性心肌梗死相关线粒体基因的生物信息学鉴定与验证  

Bioinformatics identification and validation of mitochondrial genes related to acute myocardial infarction

作　　者：田宇诗 付强 李冀[2] Tian Yushi;Fu Qiang;Li Ji(School of Basic Medicine,Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang Province,China;Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang Province,China)

机构地区：[1]黑龙江中医药大学基础医学院,黑龙江省哈尔滨市150040 [2]黑龙江中医药大学,黑龙江省哈尔滨市150040

出　　处：《中国组织工程研究》2025年第31期6697-6707,共11页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81874426),项目负责人:李冀;中医药传承与创新“百千万”人才工程(岐黄工程)岐黄学者项目(国中医药人教函[2018]284号),项目负责人:李冀。

摘　　要：背景:线粒体在急性心肌梗死损伤和修复中具有重要意义,因此基于线粒体基因探索急性心肌梗死发病进展具有重要的临床意义。目的:探究线粒体基因是否可以作为评估急性心肌梗死进展的可靠生物标志物。方法:从高通量基因表达数据库下载急性心肌梗死数据集GSE66360,GSE12288,在线粒体蛋白质数据库获取人类线粒体基因集;对急性心肌梗死数据集GSE66360进行差异基因分析及加权基因共表达网络分析,两者取交集后获得基因进行蛋白质-蛋白质相互作用分析、基因本体论和京都基因与基因组百科全书分析;将交集基因与人类线粒体基因取交集以获得差异线粒体基因,对差异线粒体基因进行基因集富集分析和免疫浸润分析,并在外部数据集GSE12288中进行受试者工作特征曲线分析,验证线粒体差异基因的表达特征。结果与结论:①获得急性心肌梗死差异基因548个,差异基因分析及加权基因共表达网络分析显示Blue模块包含基因最多(4992个),二者交集基因共有116个,其中肿瘤坏死因子、白细胞介素1B、白细胞介素6、Toll样受体4和白细胞介素10为核心基因;②基因本体论分析显示生物过程主要涉及炎症反应、肿瘤坏死因子产生的正调控及细胞表面受体信号通路,细胞组成主要涉及三级颗粒膜、质膜外层和质膜等,分子功能主要涉及免疫球蛋白G结合、跨膜信号受体活性及趋化因子活性等,京都基因与基因组百科全书分析显示,这些基因主要涉及肿瘤坏死因子、白细胞介素17及核转录因子κB通路;③共获得8个差异线粒体基因,经过最小绝对收缩和选择算子和比例风险回归模型分析后筛选出4个特征基因,包括佛波醇-12-肉豆酸酯-13-乙酰基诱导蛋白1、BCL2-相关蛋白A1、溶质载体家族25成员37和脱氧核糖核酸聚合酶β,并分别对应了肿瘤蛋白53、氧化磷酸化、硫代谢及甘油磷脂代谢通路BACKGROUND:Mitochondria are of great significance in the injury and repair of acute myocardial infarction,so it is of great clinical significance to explore the pathogenesis and progression of acute myocardial infarction based on mitochondrial genes.OBJECTIVE:To explore whether mitochondrial genes can be used as reliable biomarkers to assess the progression of acute myocardial infarction.METHODS:The acute myocardial infarction dataset was downloaded from the Gene Expression Omnibus GSE66360 and GSE12288,and the human mitochondrial gene set was obtained from the mitochondrial protein database.Differential gene analysis and weighted correlation network analysis were performed on the acute myocardial infarction dataset GSE66360,and the genes were obtained for protein-protein interaction analysis,gene ontology,and kyoto encyclopedia of genes genomes analysis.The intersection genes were intersected with human mitochondrial genes to obtain differential mitochondrial genes.Gene set enrichment analysis and immune infiltration analysis were performed on differential mitochondrial genes.Receiver operating characteristic curve analysis was performed in the external dataset GSE12288 to verify the expression characteristics of the differential mitochondrial genes.RESULTS AND CONCLUSION:(1)A total of 548 differential genes were obtained for acute myocardial infarction.Differential gene analysis and weighted gene co-expression network analysis showed that the Blue module contained the most genes(4992).There were 116 intersecting genes,among which tumor necrosis factor,interleukin-1B,interleukin-6,Toll-like receptor 4,and interleukin-10 were the core genes.(2)Gene ontology analysis showed that the biological process mainly involved inflammatory response,positive regulation of tumor necrosis factor production,cell surface receptor signaling pathway.Cell composition mainly involved tertiary granular membrane,plasma membrane outer layer,plasma membrane,etc.Molecular function mainly involved immunoglobulin G binding,transmembrane si

关 键 词：线粒体 急性心肌梗死 生物信息学 机器学习 免疫浸润分析 氧化应激 炎症 凋亡 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R542.22