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Screening and validating the immune-related gene expression signatures in peripheral blood mononuclear cells of nonischaemic cardiomyopathy

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China

Background: Mountainous evidence has revealed that an activated immune response in the heart can provoke left ventricular dysfunction and result in adverse cardiac remodelling. This study was designed to explore the potential mechanisms and identify core biomarkers in peripheral blood mononuclear cells (PBMCs) of nonischaemic cardiomyopathy (NICM). Methods: GSE9128, particularly, the samples of PBMCs from 3 control individuals and 4 NICM patients, was downloaded from the GEO database to identify differentially expressed genes (DEGs). DAVID was employed to perform gene ontology (GO) and Kyoto PBMC of Genes and Genomes (KEGG) analyses. Meanwhile, a protein-protein interaction (PPI) network was constructed to display the interactions among these DEGs. The expression of the top 5 upregulated and downregulated DEGs was validated in a NICM mice model induced by isoproterenol via real-time PCR. Results: In this study, a total of 371 DEGs (fold change > 2), consisting of 288 upregulated DEGs and 83 downregulated DEGs, were captured in the PBMCs. GO and KEGG analysis demonstrated that these DEGs were particularly enriched in inflammatory response, immune response, extracellular exosome and cell differentiation. Additionally, the hub genes with the 15 highest connectivity degrees were also identified, namely, JUN, MYC, HSP90AA1, PCNA, CREB1, IL1B, IL8, SMARCA2, TLR4, RB1, RANBP2, EGR1, PTGS2, ENO1 and XPO1. Finally, our in vitro experiment not only validated the mRNA expression levels of the top 5 upregulated and downregulated DEGs in mice but also further clarified their expression in subtypes of PBMCs. Conclusion: Our study unveiled potential biomarkers and molecular mechanisms in NICM, which could provide a non-invasive strategy for the diagnosis and treatment of NICM.
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Keywords peripheral blood mononuclear cells; nonischaemic cardiomyopathy; immune-related biomarkers; bioinformatics analysis

Citation: Ning Li, Jining Zhou. Screening and validating the immune-related gene expression signatures in peripheral blood mononuclear cells of nonischaemic cardiomyopathy. Mathematical Biosciences and Engineering, 2020, 17(3): 2330-2347. doi: 10.3934/mbe.2020124


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