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Global Translational Medicine Bioinformatics analysis of dilated cardiomyopathy

1. Introduction able to learn about mechanisms and pathways of disease
development or cancer metastasis, and can identify new
Dilated cardiomyopathy (DCM) is a disease of heart potential therapeutic targets and discover mechanisms
muscle. The enlargement of the ventricle and reduced of resistance to drugs . The Gene Expression Omnibus
[10]
systolic function without the abnormal loads is some of the (GEO) is a database for reserving and searching publicly
manifestations of DCM . Most DCM cases will eventually available data, such as high-throughput gene expression
[1]
develop into chronic heart failure. Approximately 1 data . Through bioinformatics analysis, we can analyze
[11]
in 250 – 2500 people suffers from DCM . The study gene expression profiles from the GEO database to obtain
[2]
shows that about 67% of patients eventually die of heart differentially expressed genes (DEGs) between DCM
failure and the rest die of sudden cardiac death . Child with heart failure tissues and normal function (NF) heart
[3]
mortality attributed to DCM is significantly higher than tissues. Then, the gene ontology (GO) analysis and gene set
[2]
that of adults . The manifestations, such as right heart enrichment analysis (GSEA) can be used to reveal the role
failure, pulmonary hypertension, and enlargement of both of the genes and the pathway they participate. Hub genes are
ventricles, are often indicative of a poor outcome . important in biological processes (BPs) as they often play a
[3]
The etiology of DCM is either hereditary, mixed dominant role in the pathway by regulating other genes and
(mainly non-hereditary), or acquired. Some causes such as are significant research hotspots and therapeutic targets.
infectious myocarditis, drug, and alcohol abuse often lead Protein-protein interaction (PPI) network, a network of
to DCM . But in a large percentage of cases, the etiology physical contact between two or more proteins, is involved
[4]
of DCM has not been fully identified and is classified as in biological signaling, gene expression regulation, energy
[12]
idiopathic. Idiopathic DCM is a primary heart muscle and substance metabolism, and cell cycle regulation . The
disease of unknown cause . About 30 – 50% of patients mRNA-miRNA-lncRNA network, a network formed by
[5]
with idiopathic DCM have a family history, so DCM mRNAs, miRNAs, and lncRNAs with interacting sites, plays
[13]
with family heredity is also known as familial DCM. The a post-transcriptional regulatory role . In this study, the
diagnosis of familial DCM depends on the medical history, hub genes in DCM with heart failure tissue were screened
clinical manifestations of DCM or heart failure, and with the aid of the PPI networks. Finally, the predicted
features of echocardiography, chest X-ray, cardiac magnetic mRNA-miRNA-lncRNA network was established to help
resonance imaging (MRI), and endomyocardial biopsy. uncover more potential therapeutic targets. The genes
Echocardiography of idiopathic DCM would show dilated identified in this study may have potential value in the
left ventricle and systolic dysfunction, while enlarged diagnosis and therapy of DCM at genetic level.
cardiac shadow with >50% cardiothoracic ratio is a typical
finding on X-ray. Cardiac MRI helps to identify diseases 2. Materials and methods
such as myocarditis . Endomyocardial myocardial biopsy 2.1. Data source
[6]
helps to clarify the diagnosis. The accuracy of genetic All the gene expression datasets (GSE29819, GSE57338,
testing of DCM is only 15 – 40% due to the complex GSE5406, and GSE79962) of idiopathic DCM with heart
pathogenesis . The most widely used markers are B-type failure tissues and NF heart tissues were downloaded from
[2]
natriuretic peptide and N-terminal pro-brain natriuretic the GEO database. GSE29819 and GSE57338 were used
peptide, but they are only used to reflect the level of heart as test sets. GSE29819 from GPL570: Affymetrix Human
failure and have poor diagnostic specificity . The primary Genome U133 Plus 2.0 Array includes 14 DCM samples
[7]
objectives of the DCM treatment are to treat the cause and 12 NF samples; GSE57338 from GPL11532: Affymetrix
and control fluid levels. Some of the therapeutic agents for Human Gene 1.1 ST Array includes 82 DCM samples
DCM include beta adrenoreceptor blockers, angiotensin and 136 NF samples. GSE5406 and GSE79962 served
converting enzyme inhibitors, angiotensin receptor as validation sets in this study. GSE5406 from GPL96:
blockers, and vasodilators. Cardiac resynchronization Affymetrix Human Genome U133A Array includes 86
therapy is available for patients with symptoms of heart DCM samples and 16 NF samples; and GSE79962 from
failure who have failed to receive optimal drug therapy; GPL6244: Affymetrix Human Gene 1.0 ST Array includes
eventually, heart transplantation may be considered if 9 DCM samples and 11 NF samples. All the data can be
the heart failure treatment fails . Nevertheless, genetic obtained online, and no experiments involving animals
[8]
diagnosis and treatment are lacking among the existing and humans were performed in this study.
clinical diagnostic and therapeutic tools for DCM.
Bioinformatics is a discipline involving processes that 2.2. Identification of DEGs
obtain, reserve, and visualize biological data using certain The DEGs from each datasets were analyzed by the
tools and methods . By using bioinformatics, we may be GEO2R online tool , setting the screening condition as
[9]
[14]
Volume 1 Issue 1 (2022) 2 https://doi.org/10.36922/gtm.v1i1.104