Zhang Xuemei, Cheng Xiaoshu, Liu Huifeng, Zheng Chunhua, Rao Kunrui, Fang Yi, Zhou Hairong, Xiong Shenghe
Department of Cardiology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
Department of Cardiology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
Int J Mol Med. 2014 Sep;34(3):863-9. doi: 10.3892/ijmm.2014.1817. Epub 2014 Jun 23.
The aim of this study was to identify key genes associated with coronary artery disease (CAD) and to explore the related signaling pathways. Gene expression profiles of 110 CAD and 112 non-CAD, healthy patients [CAD index (CADi) >23 and =0, respectively] were downloaded from the Gene Expression Omnibus (GEO) database (accession: GSE12288). The differentially expressed genes (DEGs) in CAD were identified using t-tests, and protein-protein interaction (PPI) networks for these DEGs were constructed using the Search Tool for the Retrieval of InteractiNg Genes (STRING) database. The Database for Annotation, Visualization and Integrated Discovery (DAVID) tool was used to identify potentially enriched biological processes (BP) among the DEGs using Gene Ontology (GO) terms, and to identify the related pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. In addition, expression-activated subnetworks (crucial modules) of the constructed PPI networks were identified using the jActiveModule plug-in, and their topological properties were analyzed using NetworkAnalyzer, both available from Cytoscape. The patient specimens were classified as grade I, II and III based on CADi values. There were 151 DEGs in grade I, 362 in grade II and 425 in grade III. In the PPI network, the gene GRB2, encoding the growth factor receptor-bound protein 2, was the only common DEG among the three grades. In addition, 10 crucial modules were identified in the PPIs, 4 of which showed significant enrichment for GO BP terms. In the 12 nodes with the highest betweenness centrality, we found two genes, encoding GRB2 and the heat shock 70 kDa protein 8 (HSPA8). Moreover, the chemokine and focal adhesion signaling pathways were selected based on their relative abundance in CAD. The GRB2 and HSPA8 proteins, as well as the chemokine and focal adhension signaling pathways, might therefore be critical for the development of CAD.
本研究旨在识别与冠状动脉疾病（CAD）相关的关键基因，并探索相关信号通路。从基因表达综合数据库（GEO）（登录号：GSE12288）下载了110例CAD患者和112例非CAD健康患者（CAD指数分别>23和=0）的基因表达谱。使用t检验识别CAD中的差异表达基因（DEG），并使用检索相互作用基因的搜索工具（STRING）数据库构建这些DEG的蛋白质-蛋白质相互作用（PPI）网络。使用注释、可视化和综合发现数据库（DAVID）工具，利用基因本体（GO）术语识别DEG中潜在富集的生物学过程（BP），并使用京都基因与基因组百科全书（KEGG）通路数据库识别相关通路。此外，使用jActiveModule插件识别构建的PPI网络的表达激活子网（关键模块），并使用Cytoscape提供的NetworkAnalyzer分析其拓扑特性。根据CAD指数值将患者标本分为I级、II级和III级。I级有151个DEG，II级有362个，III级有425个。在PPI网络中，编码生长因子受体结合蛋白2的基因GRB2是三个级别中唯一共同的DEG。此外，在PPI中识别出10个关键模块，其中4个显示出GO BP术语的显著富集。在中间中心性最高的12个节点中，我们发现了两个基因，分别编码GRB2和热休克70 kDa蛋白8（HSPA8）。此外，根据趋化因子和粘着斑信号通路在CAD中的相对丰度进行了选择。因此，GRB2和HSPA8蛋白以及趋化因子和粘着斑信号通路可能对CAD的发展至关重要。
