Abstract
Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Several studies have used RNA-sequencing (RNA-seq) to profile differentially expressed genes (DEGs) associated with DCM. In this study, we aimed to profile gene expression signatures and identify novel genes associated with DCM through a quantitative meta-analysis of three publicly available RNA-seq studies using human left ventricle tissues from 41 DCM cases and 21 control samples. Our meta-analysis identified 789 DEGs including 581 downregulated and 208 upregulated genes. Several DCM-related genes previously reported, including MYH6, CKM, NKX2–5 and ATP2A2, were among the top 50 DEGs. Our meta-analysis also identified 39 new DEGs that were not detected using those individual RNA-seq datasets. Some of those genes, including PTH1R, ADAM15 and S100A4, confirmed previous reports of associations with cardiovascular functions. Using DEGs from this meta-analysis, the Ingenuity Pathway Analysis (IPA) identified five activated toxicity pathways, including failure of heart as the most significant pathway. Among the upstream regulators, SMARCA4 was downregulated and prioritized by IPA as the top affected upstream regulator for several DCM-related genes. To our knowledge, this study is the first to perform a transcriptomic meta-analysis for clinical DCM using RNA-seq datasets. Overall, our meta-analysis successfully identified a core set of genes associated with DCM.
Highlights
Cardiovascular diseases are the leading cause of death in the United States and accounted for840,000 deaths in 2016 [1]
We performed a quantitative meta-analysis of three independent RNA-seq studies using human left ventricle tissues to identify robust candidate biomarkers for Dilated cardiomyopathy (DCM)
Our meta-analysis identified 789 differentially expressed genes (DEGs) including 581 downregulated and 208 upregulated genes at a false discovery rate (FDR) < 0.05 (Supplementary Table S1)
Summary
Cardiovascular diseases are the leading cause of death in the United States and accounted for840,000 deaths in 2016 [1]. Cardiovascular diseases are the leading cause of death in the United States and accounted for. Heart failure is among the cardiovascular diseases with a high risk of death and with other adverse symptoms along with poor quality of life. It limits daily physical and social activities and leads to various physical and emotional distress [2]. DCM is an irreversible form of heart muscle disease and is characterized as left ventricle enlargement and systolic dysfunction. Decline in left ventricle contractile function can cause inefficient blood pumping and heart weakness, eventually leading to sudden or heart failure-related death [3]
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