title: Identification of key genes and crucial modules associated with coronary artery disease by bioinformatics analysis.
abstract: 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.
authors: Department of Cardiology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
authors: Xuemei
authors: X
authors: Zhang
authors: Department of Cardiology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
authors: Xiaoshu
authors: X
authors: Cheng
authors: Department of Cardiology, Xiaolan People's Hospital, Zhongshan, Guangdong 528415, P.R. China.
authors: Huifeng
authors: H
authors: Liu
authors: Department of Cardiology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
authors: Chunhua
authors: C
authors: Zheng
authors: Department of Cardiology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
authors: Kunrui
authors: K
authors: Rao
authors: Department of Cardiology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
authors: Yi
authors: Y
authors: Fang
authors: Department of Cardiology, Second People's Hospital, Mudanjiang, Heilongjiang 157000, P.R. China.
authors: Hairong
authors: H
authors: Zhou
authors: Department of Cardiology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China.
authors: Shenghe
authors: S
authors: Xiong
mesh_terms: D018925:Chemokines / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D003324:Coronary Artery Disease / Q000235:genetics*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D060066:Protein Interaction Maps; D015398:Signal Transduction / Q000235:genetics; D012984:Software
chemical_list: D018925:Chemokines