Objective   To explore the differential expression genes of coronary artery disease by gene set enrichment analysis and weighted gene co-expression network analysis and excavate key genes associated with the development of coronary artery disease.

  Methods   The GSE71226 dataset was downloaded from the Gene Expression Omnibus database of the National Center for Biotechnology Information (NCBI), and the differential genes of coronary artery disease were screened and the enrichment analysis was performed. The gene set enrichment analysis was performed on the differential genes to screen for microRNAs (miRNAs) associated with differential expression genes in coronary artery disease, and the regulation network was constructed. The gene co-expression modules were constructed based on the correlation of genes, and the correlation between gene modules and clinical information was calculated. The genes of modules significantly correlating with clinical phenotypes were selected to construct protein-protein interaction network for screening of the core genes.

  Results   After screening, a total of 130 differential expression genes in coronary artery disease were obtained, enriched in signaling pathways such as Hippo, fluid shear stress and atherosclerosis, adenosine monophosphate-dependent protein kinase (AMPK), Wnt, nucleotide-binding oligomerization domain (NOD) like receptors and interleukin 17. Enrichment analysis showed that the miRNAs such as miR-503-3p, miR-3674, miR -5088-5p and miR-4486 were closely related to coronary artery disease. Based on the correlation of gene expression, 10 co-expression modules were obtained, and the magenta module was significantly associated with the development of coronary artery disease. Topological analysis showed that BMP4 and C3 were the core genes of the protein-protein interaction network.

  Conclusion   There are significant differences in gene expressions during the pathogenesis of coronary artery disease, the pathological process involves multiple targets and pathways, and pathogenesis involving in multiple targets and pathways may be regulated by multiple miRNAs. BMP4 and C3 may be the core genes in the pathogenesis of coronary artery disease.