联合生物信息学分析鉴定不稳定粥样硬化斑块中的枢纽基因

Identification of hub genes in unstable atherosclerotic plaque by conjoint analysis of bioinformatics.

机构信息

Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, PR China.

出版信息

Life Sci. 2020 Dec 1;262:118517. doi: 10.1016/j.lfs.2020.118517. Epub 2020 Oct 1.

DOI:10.1016/j.lfs.2020.118517

PMID:33011223

Abstract

AIMS

Unstable atherosclerotic plaque is the main pathological basis of acute coronary syndrome, which is the leading cause of death and disability worldwide. Therefore, we combined multiple bioinformatics tools to identify key genes related to unstable plaque.

MAIN METHODS

GSE94605 contained 7 plasma sample pools of 175 healthy and 6 sample pools of 150 unstable angina pectoris (UAP) patients, and detected with miRNA array while GSE60993 collected peripheral blood from 7 normal and 9 UAP, and detected with mRNA array. GSE120521 collected carotid plaques from 4 patients and dissected in stable and unstable regions, then detected with RNA-seq. Differentially expressed miRNAs (DEMs) and genes (DEGs) in UAP were re-analyzed. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network were applied on top 10 up-regulated or down-regulated DEMs targets, and whole DEGs. MiRNAs-mRNAs network was constructed with these DEMs and DEGs, and the expression profile of genes within the network was finally validated in GSE120521.

KEY FINDINGS

Totally, 263 up-regulated and 201 down-regulated DEMs were identified in GSE94605, and 78 up-regulated and 29 down-regulated DEGs were identified in GSE60993. Subsequently, a miRNAs-mRNAs network was constructed with 6 up-regulated miRNAs targeted to 12 down-regulated genes, and 4 down-regulated miRNAs targeted to 8 up-regulated genes. Finally, MORF4L2, RAB3IL1 and MMP9 within the network were considered as hub genes in unstable plaque progression after being validated in GSE120521.

SIGNIFICANCE

These 3 genes may provide new targets for diagnosis and therapy of unstable atherosclerotic plaque.

摘要

目的

不稳定的动脉粥样硬化斑块是急性冠状动脉综合征的主要病理基础，也是全球范围内导致死亡和残疾的主要原因。因此，我们结合了多种生物信息学工具来识别与不稳定斑块相关的关键基因。

方法

GSE94605 包含了 7 个健康人血浆样本池（175 例）和 6 个不稳定型心绞痛（UAP）患者样本池（150 例），采用 miRNA 芯片进行检测；GSE60993 收集了 7 个正常人外周血和 9 个 UAP 患者外周血，采用 mRNA 芯片进行检测；GSE120521 收集了 4 例颈动脉斑块，分别取自稳定区和不稳定区，采用 RNA-seq 进行检测。对 UAP 中的差异表达 miRNA（DEMs）和基因（DEGs）进行重新分析。对 top10 上调或下调的 DEMs 靶基因和全 DEGs 进行基因本体论（GO）/京都基因与基因组百科全书（KEGG）和蛋白-蛋白相互作用（PPI）网络分析。用这些 DEMs 和 DEGs 构建 miRNA-mRNAs 网络，最后在 GSE120521 中验证网络内基因的表达谱。

主要发现

在 GSE94605 中鉴定出 263 个上调的 DEMs 和 201 个下调的 DEMs，在 GSE60993 中鉴定出 78 个上调的 DEGs 和 29 个下调的 DEGs。随后，构建了一个由 6 个上调的 miRNA 靶向 12 个下调基因和 4 个下调的 miRNA 靶向 8 个上调基因组成的 miRNA-mRNAs 网络。最后，在 GSE120521 中验证后，网络内的 MORF4L2、RAB3IL1 和 MMP9 被认为是不稳定斑块进展的枢纽基因。