Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis

BackgroundAtrial fibrillation (AF) is a serious complication of dilated cardiomyopathy (DCM), which increases the risk of thromboembolic events and sudden death in DCM patients. However, the common mechanism of DCM combined with AF remains unclear. This study aims to explore the molecular mechanism...

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Main Authors: Ting Gan, Jing Hu, Anwer Khalid Okab Aledan, Wenhu Liu, Cui Li, Shuai Lu, Ya Wang, Qian Xu, Yan Wang, Zhaohui Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049351/full
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author Ting Gan
Ting Gan
Ting Gan
Jing Hu
Anwer Khalid Okab Aledan
Anwer Khalid Okab Aledan
Anwer Khalid Okab Aledan
Wenhu Liu
Wenhu Liu
Wenhu Liu
Cui Li
Cui Li
Cui Li
Shuai Lu
Ya Wang
Ya Wang
Ya Wang
Qian Xu
Qian Xu
Qian Xu
Yan Wang
Yan Wang
Yan Wang
Zhaohui Wang
Zhaohui Wang
Zhaohui Wang
author_facet Ting Gan
Ting Gan
Ting Gan
Jing Hu
Anwer Khalid Okab Aledan
Anwer Khalid Okab Aledan
Anwer Khalid Okab Aledan
Wenhu Liu
Wenhu Liu
Wenhu Liu
Cui Li
Cui Li
Cui Li
Shuai Lu
Ya Wang
Ya Wang
Ya Wang
Qian Xu
Qian Xu
Qian Xu
Yan Wang
Yan Wang
Yan Wang
Zhaohui Wang
Zhaohui Wang
Zhaohui Wang
author_sort Ting Gan
collection DOAJ
description BackgroundAtrial fibrillation (AF) is a serious complication of dilated cardiomyopathy (DCM), which increases the risk of thromboembolic events and sudden death in DCM patients. However, the common mechanism of DCM combined with AF remains unclear. This study aims to explore the molecular mechanism and analyze immune infiltration in DCM complicated with AF through comprehensive bioinformatics analysis.MethodsThe gene expression datasets of DCM (GSE141910) and AF (GSE41177 and GSE79768) were obtained from the Gene Expression Omnibus database. Gene enrichment analyses were performed after screening the common differentially expressed genes (DEGs) of DCM and AF. Protein-protein interaction network was constructed in the STRING database and visualized in Cytoscape software, which helped to further screen the central functional modules of DEGs and hub genes. In addition, ImmuCellAI algorithm was performed to estimate immune infiltration patterns, and Spearman correlation was conducted to investigate the correlation between the abundance of multiple immune cells and the expression levels of hub immune-related genes after obtaining hub immune-related genes from the ImmPort database. The hub immune-related genes expression and immune infiltration patterns were additionally verified in the validation datasets (GSE57338, GSE115574, and GSE31821). The diagnostic effectiveness of hub immune-related genes was evaluated through Receiver Operator Characteristic Curve analysis.ResultsA total of 184 common DEGs in DCM and AF were identified for subsequent analyses. The functions of hub genes were significantly associated with immune responses. We identified 7 hub immune-related genes (HLA-DRA, LCK, ITK, CD48, CD247, CD3D, and IL2RG) and a spectrum of immune cell subsets including Monocyte, Neutrophil, and follicular helper T (Tfh) cells were found to be concurrently dysregulated in both DCM and AF. 7 hub immune-related genes were predominantly favorably correlated with Tfh cells and were primarily negatively correlated with Neutrophil infiltrations in DCM and AF. CD48+CD3D were verified to diagnose DCM and AF with excellent sensitivity and specificity, showing favorable diagnostic value.ConclusionsOur study reveals that immune cells (Tfh cells) disorders caused by hub immune-related genes (CD48 and CD3D) may be the common pathogenesis of DCM combined with AF, which lays a foundation for further immune mechanism research.
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spelling doaj.art-5246affa91ee45bb8e577092059e2ee92023-01-17T04:45:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.10493511049351Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysisTing Gan0Ting Gan1Ting Gan2Jing Hu3Anwer Khalid Okab Aledan4Anwer Khalid Okab Aledan5Anwer Khalid Okab Aledan6Wenhu Liu7Wenhu Liu8Wenhu Liu9Cui Li10Cui Li11Cui Li12Shuai Lu13Ya Wang14Ya Wang15Ya Wang16Qian Xu17Qian Xu18Qian Xu19Yan Wang20Yan Wang21Yan Wang22Zhaohui Wang23Zhaohui Wang24Zhaohui Wang25Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaBackgroundAtrial fibrillation (AF) is a serious complication of dilated cardiomyopathy (DCM), which increases the risk of thromboembolic events and sudden death in DCM patients. However, the common mechanism of DCM combined with AF remains unclear. This study aims to explore the molecular mechanism and analyze immune infiltration in DCM complicated with AF through comprehensive bioinformatics analysis.MethodsThe gene expression datasets of DCM (GSE141910) and AF (GSE41177 and GSE79768) were obtained from the Gene Expression Omnibus database. Gene enrichment analyses were performed after screening the common differentially expressed genes (DEGs) of DCM and AF. Protein-protein interaction network was constructed in the STRING database and visualized in Cytoscape software, which helped to further screen the central functional modules of DEGs and hub genes. In addition, ImmuCellAI algorithm was performed to estimate immune infiltration patterns, and Spearman correlation was conducted to investigate the correlation between the abundance of multiple immune cells and the expression levels of hub immune-related genes after obtaining hub immune-related genes from the ImmPort database. The hub immune-related genes expression and immune infiltration patterns were additionally verified in the validation datasets (GSE57338, GSE115574, and GSE31821). The diagnostic effectiveness of hub immune-related genes was evaluated through Receiver Operator Characteristic Curve analysis.ResultsA total of 184 common DEGs in DCM and AF were identified for subsequent analyses. The functions of hub genes were significantly associated with immune responses. We identified 7 hub immune-related genes (HLA-DRA, LCK, ITK, CD48, CD247, CD3D, and IL2RG) and a spectrum of immune cell subsets including Monocyte, Neutrophil, and follicular helper T (Tfh) cells were found to be concurrently dysregulated in both DCM and AF. 7 hub immune-related genes were predominantly favorably correlated with Tfh cells and were primarily negatively correlated with Neutrophil infiltrations in DCM and AF. CD48+CD3D were verified to diagnose DCM and AF with excellent sensitivity and specificity, showing favorable diagnostic value.ConclusionsOur study reveals that immune cells (Tfh cells) disorders caused by hub immune-related genes (CD48 and CD3D) may be the common pathogenesis of DCM combined with AF, which lays a foundation for further immune mechanism research.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049351/fulldilated cardiomyopathyatrial fibrillationbioinformaticsdifferentially expressed geneshub immune-related genesimmune infiltration
spellingShingle Ting Gan
Ting Gan
Ting Gan
Jing Hu
Anwer Khalid Okab Aledan
Anwer Khalid Okab Aledan
Anwer Khalid Okab Aledan
Wenhu Liu
Wenhu Liu
Wenhu Liu
Cui Li
Cui Li
Cui Li
Shuai Lu
Ya Wang
Ya Wang
Ya Wang
Qian Xu
Qian Xu
Qian Xu
Yan Wang
Yan Wang
Yan Wang
Zhaohui Wang
Zhaohui Wang
Zhaohui Wang
Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis
Frontiers in Immunology
dilated cardiomyopathy
atrial fibrillation
bioinformatics
differentially expressed genes
hub immune-related genes
immune infiltration
title Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis
title_full Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis
title_fullStr Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis
title_full_unstemmed Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis
title_short Exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis
title_sort exploring the pathogenesis and immune infiltration in dilated cardiomyopathy complicated with atrial fibrillation by bioinformatics analysis
topic dilated cardiomyopathy
atrial fibrillation
bioinformatics
differentially expressed genes
hub immune-related genes
immune infiltration
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049351/full
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