Construction and Evaluation of Immune-related Diagnostic Model in Patients with Heart Failure Caused by Idiopathic Dilated Cardiomyopathy

Overview

Journal BMC Cardiovasc Disord

Publisher Biomed Central

Specialty Cardiology & Vascular Diseases

Date 2024 Feb 6

PMID 38321374

Authors

Sichi Xu

Zhaogui Wu

Haihua Chen

Affiliations

Soon will be listed here.

Abstract

Objective: The purpose of the study was to construct the potential diagnostic model of immune-related genes during the development of heart failure caused by idiopathic dilated cardiomyopathy.

Method: GSE5406 and GSE57338 were downloaded from the GEO website ( https://www.ncbi.nlm.nih.gov/geo/ ). CIBERSORT was used for the evaluation of immune infiltration in idiopathic dilated cardiomyopathy (DCM) of GSE5406. Differently expressed genes were calculated by the limma R package and visualized by the volcano plot. The immune-related genes were downloaded from Immport, TISIDB, and InnateDB. Then the immune-related differential genes (IRDGs) were acquired from the intersection. Protein-protein interaction network (PPI) and Cytoscape were used to visualize the hub genes. Three machine learning methods such as random forest, logical regression, and elastic network regression model were adopted to construct the prediction model. The diagnostic value was also validated in GSE57338.

Results: Our study demonstrated the obvious different ratio of T cell CD4 memory activated, T cell regulatory Tregs, and neutrophils between DCM and control donors. As many as 2139 differential genes and 274 immune-related different genes were identified. These genes were mainly enriched in lipid and atherosclerosis, human cytomegalovirus infection, and cytokine-cytokine receptor interaction. At the same time, as many as fifteen hub genes were identified as the IRDGs (IFITM3, IFITM2, IFITM1, IFIT3, IFIT1, HLA-A, HLA-B, HLA-C, ADAR, STAT1, SAMHD1, RSAD2, MX1, ISG20, IRF2). Moreover, we also discovered that the elastic network and logistic regression models had a higher diagnostic value than that of random forest models based on these hub genes.

Conclusion: Our study demonstrated the pivotal role of immune function during the development of heart failure caused by DCM. This study may offer new opportunities for the detection and intervention of immune-related DCM.

References

Wang E, Zhou R, Li T, Hua Y, Zhou K, Li Y . The Molecular Role of Immune Cells in Dilated Cardiomyopathy. Medicina (Kaunas). 2023; 59(7). PMC: 10385992. DOI: 10.3390/medicina59071246. View

Noutsias M, Rohde M, Goldner K, Block A, Blunert K, Hemaidan L . Expression of functional T-cell markers and T-cell receptor Vbeta repertoire in endomyocardial biopsies from patients presenting with acute myocarditis and dilated cardiomyopathy. Eur J Heart Fail. 2011; 13(6):611-8. DOI: 10.1093/eurjhf/hfr014. View

Mahon N, Madden B, Caforio A, Elliott P, Haven A, Keogh B . Immunohistologic evidence of myocardial disease in apparently healthy relatives of patients with dilated cardiomyopathy. J Am Coll Cardiol. 2002; 39(3):455-62. DOI: 10.1016/s0735-1097(01)01762-4. View

Ru B, Wong C, Tong Y, Zhong J, Zhong S, Wu W . TISIDB: an integrated repository portal for tumor-immune system interactions. Bioinformatics. 2019; 35(20):4200-4202. DOI: 10.1093/bioinformatics/btz210. View

Jiang Q, Yang G, Xiao F, Xie J, Wang S, Lu L . Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases. Front Immunol. 2021; 12:688066. PMC: 8290841. DOI: 10.3389/fimmu.2021.688066. View

Woudstra L, Juffermans L, van Rossum A, Niessen H, Krijnen P . Infectious myocarditis: the role of the cardiac vasculature. Heart Fail Rev. 2018; 23(4):583-595. PMC: 6010496. DOI: 10.1007/s10741-018-9688-x. View

Bozkurt B, Colvin M, Cook J, Cooper L, Deswal A, Fonarow G . Current Diagnostic and Treatment Strategies for Specific Dilated Cardiomyopathies: A Scientific Statement From the American Heart Association. Circulation. 2016; 134(23):e579-e646. DOI: 10.1161/CIR.0000000000000455. View

Kindermann I, Kindermann M, Kandolf R, Klingel K, Bultmann B, Muller T . Predictors of outcome in patients with suspected myocarditis. Circulation. 2008; 118(6):639-48. DOI: 10.1161/CIRCULATIONAHA.108.769489. View

Yokoyama A . Natural killer cells in dilated cardiomyopathy. Tohoku J Exp Med. 1988; 154(4):335-44. DOI: 10.1620/tjem.154.335. View

10.

Pankuweit S, Ruppert V, Maisch B . Inflammation in dilated cardiomyopathy. Herz. 2004; 29(8):788-93. DOI: 10.1007/s00059-004-2626-9. View

11.

Kolur V, Vastrad B, Vastrad C, Kotturshetti S, Tengli A . Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis. BMC Cardiovasc Disord. 2021; 21(1):329. PMC: 8256614. DOI: 10.1186/s12872-021-02146-8. View

12.

Huang G, Bisaria A, Wakefield D, Yamawaki T, Luo X, Zhang J . Titin-truncating variants in hiPSC cardiomyocytes induce pathogenic proteinopathy and sarcomere defects with preserved core contractile machinery. Stem Cell Reports. 2022; 18(1):220-236. PMC: 9860080. DOI: 10.1016/j.stemcr.2022.11.008. View

13.

Yoo M, Shin J, Kim J, Ryall K, Lee K, Lee S . DSigDB: drug signatures database for gene set analysis. Bioinformatics. 2015; 31(18):3069-71. PMC: 4668778. DOI: 10.1093/bioinformatics/btv313. View

14.

Ng D, Court N, Dos Remedios C, Bogoyevitch M . Activation of signal transducer and activator of transcription (STAT) pathways in failing human hearts. Cardiovasc Res. 2003; 57(2):333-46. DOI: 10.1016/s0008-6363(02)00664-8. View

15.

Chaffin M, Papangeli I, Simonson B, Akkad A, Hill M, Arduini A . Single-nucleus profiling of human dilated and hypertrophic cardiomyopathy. Nature. 2022; 608(7921):174-180. DOI: 10.1038/s41586-022-04817-8. View

16.

Breuer K, Foroushani A, Laird M, Chen C, Sribnaia A, Lo R . InnateDB: systems biology of innate immunity and beyond--recent updates and continuing curation. Nucleic Acids Res. 2012; 41(Database issue):D1228-33. PMC: 3531080. DOI: 10.1093/nar/gks1147. View

17.

Mason J . Myocarditis and dilated cardiomyopathy: an inflammatory link. Cardiovasc Res. 2003; 60(1):5-10. DOI: 10.1016/s0008-6363(03)00437-1. View

18.

Sakamoto R, Kotobuki Y, Iga S, Nojima S, Deno R, Hanaoka Y . Myxovirus resistance protein 1-expressing fatal myocarditis in a patient with anti-MDA5 antibody-positive dermatomyositis. Rheumatology (Oxford). 2021; 60(12):e450-e452. DOI: 10.1093/rheumatology/keab637. View

19.

Zhao L, Fu Z . Roles of Host Immunity in Viral Myocarditis and Dilated Cardiomyopathy. J Immunol Res. 2018; 2018:5301548. PMC: 5964556. DOI: 10.1155/2018/5301548. View

20.

Chen E, Tan C, Kou Y, Duan Q, Wang Z, Meirelles G . Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013; 14:128. PMC: 3637064. DOI: 10.1186/1471-2105-14-128. View