Integrated weighted gene co-expression network analysis identified that TLR2 and CD40 are related to coronary artery disease

Abstract

Background: The current research attempted to identify possible hub genes and pathways of coronary artery disease (CAD) and to detect the possible mechanisms.Methods: Array data from GSE90074 were downloaded from the Gene Expression Omnibus (GEO) database. Integrated weighted gene co-expression network analysis (WGCNA) was performed to analyze the gene module and clinical characteristics. Gene Ontology annotation, Disease Ontology and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by clusterProfiler and the DOSE package in R. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using Molecular Complex Detection to identify hub genes. Then, further functional validation of hub genes in other microarrays and population samples was performed, and survival analysis was performed to investigate the prognosis.Results: A total of 660 genes were located in three modules and associated with CAD. GO functions identified 484 biological processes, 39 cellular components, and 22 molecular functions with an adjusted P < 0.05. Approximately 38 pathways were enriched in KEGG pathway analysis, and 147 DO items were identified with an adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). There were a total of four modules with a score > 10 after PPI network analysis using the MCODE app, and two hub genes (TLR2 and CD14) were identified. Then, we validated the information from the GSE60993 dataset using the GSE59867 dataset and population samples, and we found that these two genes were associated with plaque vulnerability. These two genes varied at different time points after myocardial infarction, and both of them had the lowest prognosis of heart failure when they were expressed at low levels.Conclusion: We performed an integrated WGCNA and validated that TLR2 and CD14 were closely associated with the severity of coronary artery disease, plaque instability and the prognosis of heart failure after myocardial infarction.

Identification of the Key Genes of Immune Infiltration in Dilated Cardiomyopathy

“…The other four microarrays were used for hub gene validation: GSE3586 based on the GPL3050 platform of Human Unigene3.1 cDNA Array 37.5K v1.0, GSE5406 based on the GPL96 platform of the Affymetrix Human Genome U133A Array, GSE9800 based on the GPL887 platform of the Agilent-012097 Human 1A Microarray (V2) G4110B (Feature Number version), and GSE120895 based on the GPL570 platform of Affymetrix Human Genome U133 Plus 2.0 Array. According to the rules, GSE17800 only normalized the data without logarithmic conversion, while the data preprocessing methods of other microarrays were consistent with our previous research methods [11]. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).…”

“…In recent years, the combination of gene microarrays and bioinformatics analysis has discovered new genes associated with a variety of diseases, and these new genes can be used as biomarkers for diagnosis and prognosis [10][11][12][13]. Based on this approach, a series of genes and pathways have been found to be associated with the prediction and prognosis of dilated cardiomyopathy [14,15].…”