Cardiometabolic Medicine Center, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Cardiovascular Disease, Beijing, China.
Front Immunol. 2022 Jun 20;13:879657. doi: 10.3389/fimmu.2022.879657. eCollection 2022.
The specific mechanisms and biomarkersunderlying the progression of stable coronary artery disease (CAD) to acute myocardial infarction (AMI) remain unclear. The current study aims to explore novel gene biomarkers associated with CAD progression by analyzing the transcriptomic sequencing data of peripheral blood monocytes in different stages of CAD.
A total of 24 age- and sex- matched patients at different CAD stages who received coronary angiography were enrolled, which included 8 patients with normal coronary angiography, 8 patients with angiographic intermediate lesion, and 8 patients with AMI. The RNA from peripheral blood monocytes was extracted and transcriptome sequenced to analyze the gene expression and the differentially expressed genes (DEG). A Gene Oncology (GO) enrichment analysis was performed to analyze the biological function of genes. Weighted gene correlation network analysis (WGCNA) was performed to classify genes into several gene modules with similar expression profiles, and correlation analysis was carried out to explore the association of each gene module with a clinical trait. The dynamic network biomarker (DNB) algorithm was used to calculate the key genes that promote disease progression. Finally, the overlapping genes between different analytic methods were explored.
WGCNA analysis identified a total of nine gene modules, of which two modules have the highest positive association with CAD stages. GO enrichment analysis indicated that the biological function of genes in these two gene modules was closely related to inflammatory response, which included T-cell activation, cell response to inflammatory stimuli, lymphocyte activation, cytokine production, and the apoptotic signaling pathway. DNB analysis identified a total of 103 genes that may play key roles in the progression of atherosclerosis plaque. The overlapping genes between DEG/WGCAN and DNB analysis identified the following 13 genes that may play key roles in the progression of atherosclerosis disease: SGPP2, DAZAP2, INSIG1, CD82, OLR1, ARL6IP1, LIMS1, CCL5, CDK7, HBP1, PLAU, SELENOS, and DNAJB6.
The current study identified a total of 13 genes that may play key roles in the progression of atherosclerotic plaque and provides new insights for early warning biomarkers and underlying mechanisms underlying the progression of CAD.
稳定型冠状动脉疾病（CAD）进展为急性心肌梗死（AMI）的具体机制和生物标志物尚不清楚。本研究旨在通过分析不同 CAD 阶段外周血单核细胞的转录组测序数据，探索与 CAD 进展相关的新型基因生物标志物。
共纳入 24 例年龄和性别匹配的不同 CAD 阶段接受冠状动脉造影的患者，包括 8 例冠状动脉造影正常、8 例血管造影中间病变和 8 例 AMI。提取外周血单核细胞的 RNA，进行转录组测序，分析基因表达和差异表达基因（DEG）。进行基因本体论（GO）富集分析以分析基因的生物学功能。进行加权基因相关网络分析（WGCNA）将基因分类为具有相似表达谱的几个基因模块，并进行相关性分析以探索每个基因模块与临床特征的关联。使用动态网络生物标志物（DNB）算法计算促进疾病进展的关键基因。最后，探索不同分析方法之间的重叠基因。
WGCNA 分析共鉴定出 9 个基因模块，其中两个模块与 CAD 阶段具有最高的正相关性。GO 富集分析表明，这两个基因模块中基因的生物学功能与炎症反应密切相关，包括 T 细胞激活、细胞对炎症刺激的反应、淋巴细胞激活、细胞因子产生和凋亡信号通路。DNB 分析共鉴定出 103 个可能在动脉粥样硬化斑块进展中起关键作用的基因。DEG/WGCAN 和 DNB 分析之间的重叠基因鉴定出以下 13 个可能在动脉粥样硬化疾病进展中起关键作用的基因：SGPP2、DAZAP2、INSIG1、CD82、OLR1、ARL6IP1、LIMS1、CCL5、CDK7、HBP1、PLAU、SELENOS 和 DNAJB6。
本研究共鉴定出 13 个可能在动脉粥样硬化斑块进展中起关键作用的基因，为 CAD 进展的早期预警生物标志物和潜在机制提供了新的见解。
