Co‐expression analysis provides important module and pathways of human dilated cardiomyopathy

Xiao, Junhui; Li, Fang; Yang, Qianzhao; Zeng, Xue‐Feng; Ke, Zun‐Ping

doi:10.1002/jcp.28989

Cited by 8 publications

(7 citation statements)

References 31 publications

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“…Furthermore, we employed a bunch of methods to gain an insight into DCM, making our study more comprehensive. Compared to other studies using WGCNA or DEA alone to identify genes ( 33 , 34 ), the genes screened from two methods combined were more persuasive and valuable. These genes were not only from the key modules highly associated with DCM but also had differential expression between DCM samples and controls, which were more likely to be biomarkers in the foreseen future.…”

Section: Discussionmentioning

confidence: 89%

Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy

Zheng

Han

Yang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundDilated cardiomyopathy (DCM) is characterized by left ventricular dilatation and systolic dysfunction. The pathogenesis and etiologies of DCM remain elusive. This study aims to identify the key genes to construct a genetic diagnosis model of DCM.MethodsA total of 257 DCM samples from five independent cohorts were enrolled. The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify the key modules associated with DCM. The latent mechanisms and protein-protein interaction network underlying the key modules were further revealed. Subsequently, we developed and validated a LASSO diagnostic model in five independent cohorts.ResultsTwo key modules were identified using WGCNA. Novel mechanisms related to the extracellular, mitochondrial matrix or IL-17 signaling pathway were pinpointed, which might significantly influence DCM. Besides, 23 key genes were screened out by combining WGCNA and differential expression analysis. Based on the key genes, a genetic diagnosis model was constructed and validated using five cohorts with excellent AUCs (0.975, 0.954, 0.722, 0.850, 0.988). Finally, significant differences in immune infiltration were observed between the two groups divided by the diagnostic model.ConclusionOur study revealed several novel pathways and key genes to provide potential targets and biomarkers for DCM treatment. A key genes’ diagnosis model was built to offer a new tool for diagnosing DCM.

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Section: Discussionmentioning

confidence: 89%

Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy

Zheng

Han

Yang

et al. 2022

Front. Cardiovasc. Med.

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“…The ubiquitination-mediated proteolysis pathway degrades intracellular proteins to regulate cell activities and plays a vital role in cell proliferation and growth. Xiao et al [ 48 ] believe that the ubiquitination-mediated proteolytic pathway is one of the key factors influencing dilated cardiomyopathy. A study by Nakayama [ 49 ] showed that the ubiquitination-mediated proteolytic pathway regulates cell cycle growth factors of many malignant tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Biological Mechanism of Huang Yam in Treating Tumors and Preventing Antitumor Drug-Induced Cardiotoxicity Using Network Pharmacology and Molecular Docking Technology

Zhang

Dan

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Drugs for the treatment of tumors could result in cardiotoxicity and cardiovascular diseases. We aimed to explore the anticancer properties of Huang yam as well as its cardioprotective properties using network pharmacology and molecular docking technology. The cardiovascular targets of the major chemical components of Huang yam were obtained from the following databases: TCMSP, ETCM, and BATMAN-TCM. The active ingredients of Huang yam were obtained from SwissADME. The cardiovascular targets of antitumor drugs were obtained using GeneCards, OMIM, DrugBank, DisGeNET, and SwissTargetPrediction databases. The drug-disease intersection genes were used to construct a drug-compound-target network using Cytoscape 3.7.1. A protein-protein interaction network was constructed using Cytoscape’s BisoGenet, and the core targets of Huang yam were screened to determine their antitumor properties and identify the cardiovascular targets based on topological parameters. Potential targets were imported into the Metascape platform for GO and KEGG analysis. The results were saved and visualized using R software. The components with higher median values in the network were molecularly docked with the core targets. The network contained 10 compounds, including daucosterol, delusive, dioxin, panthogenin-B, and 124 targets, such as TP53, RPS27A, and UBC. The GO function enrichment analysis showed that there were 478 items in total. KEGG enrichment analysis showed a total of 140 main pathways associated with abnormal transcription of cancer, PI3K-Akt signaling pathway, cell cycle, cancer pathway, ubiquitination-mediated proteolysis, and other pathways. Molecular docking results showed that daucosterol, delusive, dioxin, and panthogenin-B had the highest affinity for TP53, RPS27A, and UBC. The treatment of diseases using traditional Chinese medicine encompasses multiple active ingredients, targets, and pathways. Huang yam has the potential to treat cardiotoxicity caused by antitumor drugs.

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“…The present study analyzed four DCM microarrays from GEO, which to the best of the authors' knowledge is the largest sample size that has been investigated, compared with the former researches on gene expression of DCM (6,7,33,34), using integrated bioinformatics analysis. With the establishment of a PPI network, six hub genes associated with DCM were identified, including upregulated PENK, CHRDL1, IGFBP3 and cP, as well as downregulated calu and aPol1.…”

Section: Discussionmentioning

confidence: 99%

“…Huang et al (6) analyzed 102 samples from the GEO database (GSE5406), and identified module and hub genes of differentially expressed genes (DEGs) that are related to the progression of DCM. In addition, Xiao et al (7) used RNA-Seq data (GSE116250) and gene annotation of the Ensembl database to find the key module involved in DCM, and identified five co-expression modules that may have important functions in dcM occurrence. Thus, these previous studies provide possible research directions for elucidating the pathogenesis of dcM.…”

Section: Introductionmentioning

confidence: 99%

Integrated microarray analysis to identify potential biomarkers and therapeutic targets in dilated cardiomyopathy

et al. 2020

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dilated cardiomyopathy (dcM) is a primary cardiomyopathy with high mortality. The aim of the present study was to identify the related genes in dcM. The four expression profiles (GSE17800, GSE21610, GSE42955 and GSE79962) downloaded from the Gene Expression Omnibus (GEO) database were analyzed using RankProd and metaMA R packages to identify differentially expressed genes (DEGs). DEGs were uploaded to the Database for Annotation, Visualization and Integrated Discovery (DAVID), for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. a protein-protein interaction (PPi) network of the DEGs was constructed using the STRING database. In addition, hub genes were identified using the Cytoscape plugin cytoHubba. A mouse DCM model, which established via intraperitoneal injection with doxorubicin (DOX), was used to validate the hub genes. A total of 898 DEGs were identified across the four microarrays. Furthermore, GO analysis demonstrated that these DEGs were mainly enriched in cell adhesion, negative regulation of cell proliferation, negative regulation of apoptotic process and potassium ion transport. in addition, KEGG analysis revealed that DEGs were mainly enriched in the ecM-receptor interaction, the p53 signaling pathway, cardiac muscle contraction and the hypoxia-inducible factor signaling pathway. Proenkephalin (PENK), chordin like 1 (CHRDL1), calumenin (CALU), apolipoprotein L1, insulin-like growth factor binding protein 3 (IGFBP3) and ceruloplasmin (CP) were identified as hub genes in the PPI network. Furthermore, the expression levels of PENK, CHRDL1, IGFBP3, CP and CALU in hearts with dcM were validated using a mouse model. in conclusion, the present study identified six hub genes related to dcM. Therefore, the present results may provide a potential mechanism for DCM involving these hub genes, which may serve as biomarkers for screening and diagnosis in the clinic.

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Co‐expression analysis provides important module and pathways of human dilated cardiomyopathy

Cited by 8 publications

References 31 publications

Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy

Exploring Key Genes to Construct a Diagnosis Model of Dilated Cardiomyopathy

Exploring the Biological Mechanism of Huang Yam in Treating Tumors and Preventing Antitumor Drug-Induced Cardiotoxicity Using Network Pharmacology and Molecular Docking Technology

Integrated microarray analysis to identify potential biomarkers and therapeutic targets in dilated cardiomyopathy

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