Abstract
BackgroundThis study investigated the pathways and genes involved in coronary artery disease (CAD) and the associated mechanisms.MethodsTwo array data sets of GSE19339 and GSE56885 were downloaded. The limma package was used to analyze the differentially expressed genes (DEGs) in normal and CAD specimens. Examination of DEGs through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology annotation was achieved by Database for Annotation, Visualization and Integrated Discovery (DAVID). The Cytoscape software facilitated the establishment of the protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) was performed for the significant modules.ResultsWe identified 413 DEGs (291 up-regulated and 122 down-regulated). Approximately 256 biological processes, only 1 cellular component, and 21 molecular functions were identified by GO analysis and 10 pathways were enriched by KEGG. Moreover, 264 protein pairs and 64 nodes were visualized by the PPI network. After the MCODE analysis, the top 4 high degree genes, including interleukin 1 beta (IL1B, degree = 29), intercellular adhesion molecule 1 (ICAM1, degree = 25), Jun proto-oncogene (JUN, degree = 23) and C-C motif chemokine ligand 2 (CCL2, degree = 20) had been identified to validate in RT-PCR and Cox proportional hazards regression between CAD and normals.ConclusionsThe relative expression of IL1B, ICAM1 and CCL2 was higher in CAD than in normal controls (P < 0.05–0.001), but only IL1B and CCL2 genes were confirmed after testing the gene expression in blood and/or analyzing in Cox proportional hazards regression (P < 0.05–0.001), and the proper mechanism may involve in the AGE-RAGE signaling pathway, fluid shear stress, the tumor necrosis factor (TNF) and cytokine-cytokine receptor interaction.
Highlights
This study investigated the pathways and genes involved in coronary artery disease (CAD) and the associated mechanisms
RT-qPCR results showed that the expression of IL1B, ICAM1 and C motif chemokine ligand 2 (CCL2) was higher in CAD patients than in normal controls (Fig. 7b)
We combined two different datasets of CAD to analyze their Gene Ontology (GO) enrichments, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Protein-protein interaction (PPI) networks and modules to identify four significant and reproducible genes (IL1B, ICAM1, JUN and CCL2), which showed differential expression between the patients and controls. When these genes were replicated in our CAD samples, we found that serum JUN expression levels were not significantly changed and only two genes (IL1B and CCL2) were verified through the Cox proportional hazards regression
Summary
This study investigated the pathways and genes involved in coronary artery disease (CAD) and the associated mechanisms. As the number one cause of mortality, coronary artery disease (CAD) contributes to approximately 17 million deaths every year across the world [1], and almost 700,000 deaths due to CAD are recorded annually in China [2]. To some extent reaching an agreement about the early prevention of CAD would be effective. As a practical way to identify gene expression changes, a microarray analysis may be a useful method to help in the early diagnosis of CAD [8]. Numerous previous studies reveal that microarray results are not reproducible or sensitive to the changes in information [9, 10]. Even worse, when over 50 thousand probes in a microarray
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