动脉粥样硬化斑块破裂的关键免疫相关基因和潜在治疗药物的识别  

Identification of hub immune-related genes and potential therapeutic drugs for atherosclerotic plaque rupture

作　　者：尚莎莎 陈玉善[1] 李晓辉 王建茹 SHANG Shasha;CHEN Yushan;LI Xiaohui;WANG Jianru(Heart Centre,the First Affiliated Hospital of Henan University of CM,Zhengzhou 450000,Henan,China)

机构地区：[1]河南中医药大学第一附属医院心脏中心,河南郑州450000

出　　处：《暨南大学学报（自然科学与医学版）》2022年第4期348-360,共13页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：国家自然科学基金项目(82004311);国家中医临床研究基地科研专项(2019JDZX2044)。

摘　　要：目的:本研究旨在识别可能与动脉粥样硬化斑块破裂(APR)有关的关键免疫相关基因和潜在治疗药物。方法:下载GSE41571、GSE120521和E-MTAB-2055数据集并合并为一个数据集。提取免疫相关差异表达基因(DEIRGs),并构建DEIRGs的蛋白-蛋白相互作用(PPI)网络,利用分子复合物检测(MCODE)插件筛选关键hub基因。然后,利用cMap预测靶向DEIRGs治疗AS斑块破裂的候选化合物,并将其与hub基因进行了分子对接。同时,评价了hub基因的诊断效能,并开展hub基因的单基因基因集富集分析(GSEA)。结果:共获得29个DEIRGs,筛选出8个hub基因(即CD14、CSF1R、FCER1G、FCGR3A、HCST、ITGB2、S100A9和TYROBP)。cMap预测结果显示,9个候选化合物表现出了靶向DEIRGs治疗APR的潜在作用。8个hub基因在合并数据集中的曲线下面积(area under the curves, AUCs)均大于0.7,提示其具有良好的诊断APR的效能。单基因GSEA显示,8个hub基因高表达组共同富集到了B细胞受体信号通路、趋化因子信号通路、NOD样受体信号通等16个信号通路。结论:本研究发现了8个hub基因在APR的进展过程中起关键作用,9个候选化合物表现出了靶向DEIRGs治疗APR的潜在作用,结果为后续从免疫学角度探索APR的机制及治疗提供了新的思路和切入点。Objective:Identify hub immune-related genes and potential therapeutic drugs that may associated with atherosclerotic plaque rupture(APR). Methods:The GSE41571, GSE120521, and E-MTAB-2055 datasets were downloaded and merged into a single dataset. Immune-related differentially expressed genes(DEIRGs) were extracted to construct protein-protein interaction(PPI) networks for DEIRGs. The hub genes were screened by MCODE plugin form PPI networks. Next, the cMap database was used to predict candidate compounds targeting DEIRGs for treating AS plaque rupture, and molecular docking simulations between hub genes and candidate compounds were performed. The diagnostic efficacy of the hub genes was also evaluated, and a single gene set enrichment analysis(GSEA) of the hub genes were carried out. Results: A total of 29 DEIRGs were obtained and eight hub genes were screened(CD14, CSF1 R, FCER1 G, FCGR3 A, HCST, ITGB2, S100 A9 and TYROBP). The cMap predictions showed that 9 candidate compounds exhibit the potential to target DEIRGs for APR treatment. In the merged dataset, the Area under ROC curves(AUROCs) of all eight hub genes were greater than 0.7, suggesting good diagnostic efficacy for APR. Tn the high expression group, single gene GSEA showed that 8 hub genes were collectively enriched to 16 signaling pathways including B-cell receptor signaling pathway, chemokine signaling pathway and NOD-like receptor signaling passages. Conclusion: This study identified that eight hub genes played a vital role in the progression of APR, and nine candidate compounds showed potential capacity in targeting DEIRGs for APR treatment. The results provided new ideas and entry points for subsequent exploration of the mechanisms and treatment of APR from an immunological perspective.

关 键 词：动脉粥样硬化 生物信息学 免疫相关基因 破裂动脉粥样硬化斑块 稳定动脉粥样硬化斑块 

分 类 号：R54[医药卫生—心血管疾病]