Weighed Gene Coexpression Network Analysis Screens the Potential Long Noncoding RNAs and Genes Associated with Progression of Coronary Artery Disease

Abstract

Background. Coronary artery disease (CAD) is a type of heart disease with a high morbidity rate. This study is aimed at identifying potential biomarkers closely related to the progression of CAD. Materials and Methods. A microarray dataset of GSE59867 was downloaded from a public database, Gene Expression Omnibus, which included 46 cases of stable CAD without a history of myocardial infarction (MI), 30 cases of MI without heart failure (HF), and 34 cases of MI with HF. Differentially expressed long noncoding RNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified by the limma package, and functions of DEmRNAs were annotated by Gene Ontology and KEGG pathways. In addition, weighed gene coexpression network analysis (WGCNA) was used to construct a coexpression network of DEmRNAs, and a disease-related lncRNAs-mRNAs-pathway network was constructed. Finally, the datasets of GSE61145 and GSE57338 were used to verify the expression levels of the above highly correlated candidates. Results. A total of 2362 upregulated mRNAs and 2816 downregulated mRNAs, as well as 235 upregulated lncRNAs and 113 downregulated lncRNAs were screened. These genes were significantly enriched in “cytokine-cytokine receptor interaction,” “RIG-I-like receptor signaling pathway,” and “natural killer cell-mediated cytotoxicity.” Five modules including 1201 DEmRNAs were enriched in WGCNA. A coexpression network including 19 DElncRNAs and 413 DEmRNAs was constructed. These genes were significantly enriched in “phosphatidylinositol signaling system,” “insulin signaling pathway,” and “MAPK signaling pathway”. Disease-related gene-pathway network suggested FASN in “insulin signaling pathway,” DGKZ in “phosphatidylinositol signaling system,” and TNFRSF1A in “MAPK signaling pathway” were involved in MI. Conclusion. FASN, DGKZ, and TNFRSF1A were revealed to be CAD progression-associated genes by WGCNA coexpression network analysis.