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S100A9 和 SOCS3 作为急性心肌梗死的诊断生物标志物及其与免疫浸润的关系。

S100A9 and SOCS3 as diagnostic biomarkers of acute myocardial infarction and their association with immune infiltration.

机构信息

Department of Emergency Medicine, Tianjin Medical University General Hospital.

出版信息

Genes Genet Syst. 2022 Jul 16;97(2):67-79. doi: 10.1266/ggs.21-00073. Epub 2022 Jun 9.

Abstract

Acute myocardial infarction (AMI) is one of the leading causes of death globally, with a mortality rate of over 20%. However, the diagnostic biomarkers frequently used in current clinical practice have limitations in both sensitivity and specificity, likely resulting in delayed diagnosis. This study aimed to identify potential diagnostic biomarkers for AMI and explored the possible mechanisms involved. Datasets were retrieved from the Gene Expression Omnibus. First, we identified differentially expressed genes (DEGs) and preserved modules, from which we identified candidate genes by LASSO (least absolute shrinkage and selection operator) regression and the SVM-RFE (support vector machine-recursive feature elimination) algorithm. Subsequently, we used ROC (receiver operating characteristic) analysis to evaluate the diagnostic accuracy of the candidate genes. Thereafter, functional enrichment analysis and an analysis of immune infiltration were implemented. Finally, we assessed the association between biomarkers and biological processes, infiltrated cells, clinical traits, tissues and time points. We identified nine preserved modules containing 1,016 DEGs and managed to construct a diagnostic model with high accuracy (GSE48060: AUC = 0.923; GSE66360: AUC = 0.973) incorporating two genes named S100A9 and SOCS3. Functional analysis revealed the pivotal role of inflammation; immune infiltration analysis indicated that eight cell types (monocytes, epithelial cells, neutrophils, CD8+ T cells, Th2 cells, NK cells, NKT cells and platelets) were likely involved in AMI. Furthermore, we observed that S100A9 and SOCS3 were correlated with inflammation, variably infiltrated cells, clinical traits of patients, sampling tissues and sampling time points. In conclusion, we suggested S100A9 and SOCS3 as diagnostic biomarkers of AMI and discovered their association with inflammation, infiltrated immune cells and other factors.

摘要

急性心肌梗死(AMI)是全球主要死因之一,死亡率超过 20%。然而,目前临床实践中常用的诊断生物标志物在敏感性和特异性方面都存在局限性,可能导致诊断延误。本研究旨在寻找 AMI 的潜在诊断生物标志物,并探讨其中涉及的可能机制。从基因表达综合数据库中检索数据集。首先,我们鉴定了差异表达基因(DEGs)和保存模块,然后通过 LASSO(最小绝对值收缩和选择算子)回归和 SVM-RFE(支持向量机递归特征消除)算法筛选候选基因。接着,我们使用 ROC(接受者操作特征)分析评估候选基因的诊断准确性。然后,进行功能富集分析和免疫浸润分析。最后,评估生物标志物与生物过程、浸润细胞、临床特征、组织和时间点之间的关系。我们鉴定了包含 1016 个 DEGs 的 9 个保存模块,并成功构建了一个具有高准确性的诊断模型(GSE48060:AUC=0.923;GSE66360:AUC=0.973),其中包含 S100A9 和 SOCS3 这两个基因。功能分析表明炎症起着关键作用;免疫浸润分析表明,有 8 种细胞类型(单核细胞、上皮细胞、中性粒细胞、CD8+T 细胞、Th2 细胞、NK 细胞、NKT 细胞和血小板)可能与 AMI 有关。此外,我们观察到 S100A9 和 SOCS3 与炎症、浸润的免疫细胞以及其他因素有关。综上所述,我们认为 S100A9 和 SOCS3 可作为 AMI 的诊断生物标志物,并发现它们与炎症、浸润的免疫细胞和其他因素有关。

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