Identification of hub genes in unstable atherosclerotic plaque by conjoint analysis of bioinformatics
Identification of hub genes in unstable atherosclerotic plaque by conjoint analysis of bioinformatics
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生物信息学联合分析鉴定不稳定动脉粥样硬化斑块中的枢纽基因
DOI：
10.1016/j.lfs.2020.118517
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Li Yongjun
中科院分区：
文献类型：
--
作者：
Zhang Rui;Ji Zhenjun;Yao Yuyu;Zuo Wenjie;Yang Mingming;Qu Yangyang;Su Yamin;Ma Genshan;Li Yongjun
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，是全世界死亡和残疾的主要原因。因此，我们结合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。主要方法：GSE94605包含175名健康人的7个血浆样本池和150名不稳定型心绞痛（UAP）患者的6个样本池，并用miRNA芯片进行检测；GSE60993采集了7名正常人和9名UAP的外周血，并用mRNA芯片进行检测。 GSE120521收集了4名患者的颈动脉斑块，解剖稳定和不稳定区域，然后用RNA-seq进行检测。重新分析了 UAP 中差异表达的 miRNA (DEM) 和基因 (DEG)。基因本体论 (GO)/京都基因和基因组百科全书 (KEGG) 和蛋白质-蛋白质相互作用 (PPI) 网络应用于前 10 个上调或下调的 DEM 靶标以及整个 DEG。用这些 DEM 和 DEG 构建了 MiRNAs-mRNAs 网络，网络内基因的表达谱最终在 GSE120521 中得到验证。主要发现：在 GSE94605 中总共鉴定出 263 个上调和 201 个下调的 DEM，在 GSE60993 中鉴定出 78 个上调和 29 个下调的 DEG。随后，构建了一个 miRNA-mRNA 网络，其中 6 个上调 miRNA 靶向 12 个下调基因，4 个下调 miRNA 靶向 8 个上调基因。最后，网络内的MORF4L2、RAB3IL1和MMP9在GSE120521中得到验证后被认为是不稳定斑块进展的枢纽基因。意义：这3个基因可能为不稳定动脉粥样硬化斑块的诊断和治疗提供新的靶点。
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.