心肌梗死潜在生物标志物的生物信息学研究

Bioinformatics study on potential biomarkers of myocardial infarction

  • 摘要:
    目的 基于外周血单个核细胞(PBMCs)寻找心肌梗死潜在的生物学标志物。
    方法 从基因表达综合(GEO)数据库中下载心肌梗死患者PBMCs的测序数据集GSE59867, 基于加权基因共表达网络分析(WGCNA)和差异表达基因(DEGs)探讨心肌梗死过程中的生物学变化和共同基因,并进行共同转录因子预测。通过LASSO回归分析确定关键基因,绘制受试者工作特征(ROC)曲线,评估关键基因的临床价值。通过基因集富集分析(GSEA)探讨与关键基因有关的生物学变化,并基于心肌梗死数据集GSE123342验证关键基因的表达。
    结果 心肌梗死过程伴随着免疫炎症反应,其中关键基因有6个,即CD163RNASE2HPFAM20AMCEMP1FAM198B。ROC曲线分析结果显示,这些关键基因的表达对心肌梗死均有较高的诊断价值。在心肌梗死恢复过程中,这些基因的表达呈现明显下降趋势。GSEA结果显示,这些关键基因涉及的生物学改变大多与糖脂代谢、活性氧、免疫炎症等有关。
    结论 基于PBMCs进行分析,本研究发现CD163RNASE2HPFAM20AMCEMP1FAM198B基因与心肌梗死有关,这可能为心肌梗死的早期诊断和梗死恢复的监测、评估与管理提供新的见解。

     

    Abstract:
    Objective To find potential biomarkers of myocardial infarction from the perspective of peripheral blood mononuclear cells (PBMCs).
    Methods The sequencing dataset GSE59867 of peripheral blood mononuclear cells from patients with myocardial infarction was downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network (WGCNA) and differentially expressed genes (DEGs) were used to investigate the biological changes during process of myocardial infarction and to find common genes. Common transcription factors for these genes were predicted. Finally, hub genes were identified by LASSO regression analysis. Receiver operating characteristic curve (ROC) analysis was used to evaluate the clinical value of hub genes. Gene set enrichment analysis (GSEA) was used to explore the biological changes related to hub genes, and the expression of hub genes was verified based on myocardial infarction dataset GSE123342.
    Results Myocardial infarction was accompanied by an immune inflammatory response. Six novel hub genes were identified (CD163, RNASE2, HP, FAM20A, MCEMP1, and FAM198B). ROC analysis showed that the expression of these hub genes had good diagnostic for myocardial infarction. The expression of these genes also decreased significantly during recovery from infarction during recovering from myocardial infarction. GSEA results suggested that most of these hub genes were related to glucose and lipid metabolism, reactive oxygen species, immune inflammation and so on.
    Conclusion Based on the analysis of PBMCs, this study find that CD163, RNASE2, HP, FAM20A, MCEMP1 and FAM198B genes are associated with myocardial infarction, which may provide new insights for the early diagnosis of myocardial infarction and the monitoring, evaluation and management of infarction recovery.

     

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