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

Abstract

<jats:p><jats:italic>Background</jats:italic>. 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. <jats:italic>Materials and Methods</jats:italic>. 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. <jats:italic>Results</jats:italic>. 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 <jats:italic>FASN</jats:italic> in “insulin signaling pathway,” <jats:italic>DGKZ</jats:italic> in “phosphatidylinositol signaling system,” and <jats:italic>TNFRSF1A</jats:italic> in “MAPK signaling pathway” were involved in MI. <jats:italic>Conclusion</jats:italic>. <jats:italic>FASN</jats:italic>, <jats:italic>DGKZ</jats:italic>, and <jats:italic>TNFRSF1A</jats:italic> were revealed to be CAD progression-associated genes by WGCNA coexpression network analysis.</jats:p>

Risk Prediction of Cardiovascular Events by Exploration of Molecular Data with Explainable Artificial Intelligence

“…Network inference. Although differential expression analysis is a rather routine approach to obtain a list of biomarker candidates for understanding molecular disease processes, analyses involving molecular networks facilitate identification of more robust biomarkers and causal mechanisms [ 75 , 99 , 100 , 101 , 102 , 103 ]. By reverse-engineering disease-specific regulatory networks or pathways, for instance in a multi-omics setting, it is possible to trace the effects of a disease-associated genetic variant throughout the cell [ 104 ] ( Figure 1 ).…”

“…A recent study investigated gene expression microarray data from CAD patients without a history of MI, patients with MI but without heart failure, and patients with MI and heart failure (46, 34, and 30 cases, respectively) [ 102 ]. After detecting differentially expressed genes and long-non-coding RNAs (lncRNAs) between the three groups, the authors applied GO and KEGG pathway enrichment analysis to annotate the identified genes with their biological context.…”

“…Moreover, one can identify disease association on a pathway level, which might be neglected when only analyzing individual genes. In fact, many of the studies referred to above which involve network inference rely on such knowledge to verify their biomarker candidates through enrichment analyses [ 97 , 102 , 106 ].…”

Identification of vital modules and genes associated with heart failure based on weighted gene coexpression network analysis

“…Chang et al reported that tetrahydrobiopterin reverses left ventricular hypertrophy and diastolic dysfunction in spontaneously hypertensive rats through PI3K/Akt. 22 It has been reported that the MAPK signalling pathway is involved in coronary artery disease 23 and that adriamycin induces HF via the MAPK/AMPK pathway. 24 Moreover, cardiac contractility modulation has been shown to alleviate chronic HF in a rabbit model through the PI3K/ AKT pathway.…”

Potential Regulatory Role of lncRNA-miRNA-mRNA in Coronary Artery Disease (CAD)

“…4) Molecular biology studies have shown that several genes like long noncoding RNA (lncRNA) and messenger RNA (mRNA) are related to the occurrence and development of CAD. 5,6) mRNA is generally considered to be regulated by microRNA (miRNA), which is commonly used in studying various diseases (including CAD). In addition, lncRNA was more stable than mRNA.…”