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目的 旨在确定诊断急性心肌梗死(AMI)新型分子标志物,并分析免疫细胞浸润在AMI中的病理学意义。方法 从基因表达综合数据库(GEO)下载两套稳定型冠状动脉疾病(SCAD)和ST段抬高型心肌梗死(STEMI)样本数据集(GSE59867和GSE62646)。通过GSE59867数据集进行差异表达基因分析、加权基因共表达网络分析(WGCNA)、蛋白质-蛋白质相互作用(PPI)网络和3种机器学习算法[最小绝对收缩和选择算子(LASSO)、支持向量机(SVM)和随机森林(RF)]识别STEMI特异性基因。GSE62646及自测样本数据集验证STEMI特异性基因表达水平。使用ss GSEA算法量化GSE59867数据集中29种免疫细胞浸润丰度并分析与STEMI特异性基因的相关性。基于STEMI特异性基因建立Nomogram模型。结果 共鉴定出174个差异表达基因(DEGs),联合WGCNA后鉴定出95个候选基因,富集分析结果显示生物学功能和信号通路集中富集在免疫-炎症反应中。LASSO、SVM和RF算法共识别出6种STEMI特异性基因:跨膜4域亚家族A成员(MS4A)3,Mer原癌基因酪氨酸激酶(MERTK),稳定素(STAB)1,跨膜4域(MS4)A4A,CD163和趋化因子CC基序配体(CCL)4。GSE59867、GSE62646和自测样本外部数据集均显示STEMI患者外周血MS4A3明显低于SCAD患者,CCL4、CD163、MERTK、MS4A4A和STAB1表达明显高于SCAD患者(P<0.05)。STEMI患者趋化因子受体、树突细胞、炎症促进、巨噬细胞、中性粒细胞、副炎症、T型辅助细胞浸润丰度明显高于SCAD患者(P<0.05),而B细胞、CD8~+T细胞、溶细胞活性、肥大细胞、主要组织相容性复合体(MHC)Ⅰ类、NK细胞、浆细胞样树突细胞、T细胞共抑制、T细胞共刺激、Th1细胞、Th2细胞、肿瘤浸润淋巴细胞、调节性T细胞浸润丰度明显低于SCAD患者(P<0.05)。整合6种STEMI特异性基因,构建Nomogram模型构量化STEMI风险,其校准曲线显示C指数为0.896,临床影响曲线显示风险阈值在60%时,Nomogram模型所识别的高风险STEMI患者与实际观察结果趋近一致;决策曲线分析显示模型能提供显著的临床净收益。结论 MS4A3、MERTK、STAB1、MS4A4A、CD163和CCL4被确定为AMI的新型分子标志物,为其诊断和治疗提供新见解。
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基本信息:
中图分类号:R542.22
引用信息:
[1]王星,张妍,张明磊,等.基于生物信息学分析急性心肌梗死新型分子标志物及临床验证[J].中国老年学杂志,2026,46(17):3077-3085.
2026-09-08
2026-09-08