Identification and Validation of Key Gene Modules and Pathways in Coronary Artery Disease Development and Progression.

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Critical Reviews in Eukaryotic Gene Expression Pub Date : 2023-01-01 DOI:10.1615/CritRevEukaryotGeneExpr.2023039631
Ewnji Yoon, Wenjing Zhang, Yunpeng Cai, Changnong Peng, Daxin Zhou
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Abstract

The development and progression of atherosclerosis represent a chronic process involving complex molecular interactions. Therefore, identifying the potential hub genes and pathways contributing to coronary artery disease (CAD) development is essential for understanding its underlying molecular mechanisms. To this end, we performed transcriptome analysis of peripheral venous blood collected from 100 patients who were divided into four groups according to disease severity, including 27 patients in the atherosclerosis group, 22 patients in the stable angina group, 35 patients in the acute myocardial infarction group, and 16 controls. Weighted gene co-expression network analysis was performed using R programming. Significant module-trait correlations were identified according to module membership and genetic significance. Metascape was used for the functional enrichment of differentially expressed genes between groups, and the hub genes were identified via protein-protein interaction network analysis. The hub genes were further validated by analyzing Gene Expression Omnibus (GSE48060 and GSE141512) datasets. A total of 9,633 messenger ribonucleic acids were detected in three modules, among which the blue module was highly correlated with the Gensini score. The hub genes were significantly enriched in the myeloid leukocyte activation pathway, suggesting its important role in the progression of atherosclerosis. Among these genes, the Mediterranean fever gene (MEFV) may play a key role in the progression of atherosclerosis and CAD severity.

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冠状动脉疾病发生和发展的关键基因模块和途径的鉴定和验证。
动脉粥样硬化的发生和发展是一个涉及复杂分子相互作用的慢性过程。因此,识别潜在的中枢基因和促进冠状动脉疾病(CAD)发展的途径对于了解其潜在的分子机制至关重要。为此,我们对100例患者采集的外周静脉血进行转录组分析,根据病情严重程度将患者分为4组,动脉粥样硬化组27例,稳定期心绞痛组22例,急性心肌梗死组35例,对照组16例。采用R编程进行加权基因共表达网络分析。根据模块隶属度和遗传显著性鉴定出显著的模块-性状相关性。利用metscape对组间差异表达基因进行功能富集,通过蛋白-蛋白互作网络分析鉴定中心基因。通过分析Gene Expression Omnibus (GSE48060和GSE141512)数据集进一步验证中心基因。3个模块共检测到9633条信使核糖核酸,其中蓝色模块与Gensini评分高度相关。中枢基因在髓系白细胞激活通路中显著富集,提示其在动脉粥样硬化的进展中起重要作用。在这些基因中,地中海热基因(MEFV)可能在动脉粥样硬化和冠心病严重程度的进展中发挥关键作用。
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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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