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Identification of key genes and crucial modules associated with coronary artery disease by bioinformatics analysis

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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.
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Document Type: Research Article

Affiliations: 1: Department of Cardiology, Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China 2: Department of Cardiology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, P.R. China 3: Department of Cardiology, Xiaolan People's Hospital, Zhongshan, Guangdong 528415, P.R. China 4: Department of Cardiology, Second People's Hospital, Mudanjiang, Heilongjiang 157000, P.R. China

Publication date: January 1, 2014

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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