cfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients

Abstract Myocarditis is inflammatory injury of the myocardium and causes approximately 30,000 deaths globally each year. Fulminant myocarditis is an extremely severe form of myocarditis. Currently, the clinical evaluation of myocarditis and fulminant myocarditis is primarily based on symptoms, ECG f...

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Main Authors: Yangchao Zhao, Yujia Wang, Xi Zhao, Xin Zhang, Haoyan Wang, Liang Cui, Huifen Wang, Weiwei Zhu, Boyan Li, Yanjun Zhou, Jun Li, Guowei Fu, Yiheng Zhou, Pengwei Sun, Jing Bai, Xuefeng Xia, Xin Yi, Ling Yang, Chaoqun Chen, Junnan Tang, Ang Li, Zujiang Yu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Clinical Epigenetics
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Online Access:https://doi.org/10.1186/s13148-025-01914-z
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author Yangchao Zhao
Yujia Wang
Xi Zhao
Xin Zhang
Haoyan Wang
Liang Cui
Huifen Wang
Weiwei Zhu
Boyan Li
Yanjun Zhou
Jun Li
Guowei Fu
Yiheng Zhou
Pengwei Sun
Jing Bai
Xuefeng Xia
Xin Yi
Ling Yang
Chaoqun Chen
Junnan Tang
Ang Li
Zujiang Yu
author_facet Yangchao Zhao
Yujia Wang
Xi Zhao
Xin Zhang
Haoyan Wang
Liang Cui
Huifen Wang
Weiwei Zhu
Boyan Li
Yanjun Zhou
Jun Li
Guowei Fu
Yiheng Zhou
Pengwei Sun
Jing Bai
Xuefeng Xia
Xin Yi
Ling Yang
Chaoqun Chen
Junnan Tang
Ang Li
Zujiang Yu
author_sort Yangchao Zhao
collection DOAJ
description Abstract Myocarditis is inflammatory injury of the myocardium and causes approximately 30,000 deaths globally each year. Fulminant myocarditis is an extremely severe form of myocarditis. Currently, the clinical evaluation of myocarditis and fulminant myocarditis is primarily based on symptoms, ECG findings, and biochemical markers. Cardiac magnetic resonance and endomyocardial biopsy can provide further support for the diagnosis, but both have limitations in routine practice. Recent studies have shown that cell-free DNA (cfDNA) has distinct methylation patterns depending on the organ of origin, suggesting new possibilities for tracking specific types of organ damage. The core mechanism of fulminant myocarditis is a cytokine storm, leading to multiorgan damage, differing from clinically suspected myocarditis. We performed Genome-wide cfDNA methylation detection on plasma from 20 healthy donors and 22 patients (fulminant myocarditis: clinically suspected myocarditis = 9:13, COVID-19 positive: COVID-19 negative = 14:8) and found that cfDNA can be used to specifically identify early multiorgan damage caused by fulminant myocarditis, and its AUC is superior to traditional biochemical indicators such as troponin, high-sensitivity troponin, and lactate dehydrogenase. This is critically important for the timely clinical recognition and treatment of this condition. Furthermore, our study findings suggest that SARS-CoV-2 infection may exacerbate the severity of myocarditis and multiorgan damage. In summary, cfDNA shows great potential as a noninvasive, early, and sensitive biomarker for reflecting disease severity and systemic injury in fulminant myocarditis, which may help guide earlier risk stratification and intervention.
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spelling doaj-art-e32ad70e21fc4e25900f33a3ba8304032025-08-20T03:47:14ZengBMCClinical Epigenetics1868-70832025-06-0117111310.1186/s13148-025-01914-zcfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patientsYangchao Zhao0Yujia Wang1Xi Zhao2Xin Zhang3Haoyan Wang4Liang Cui5Huifen Wang6Weiwei Zhu7Boyan Li8Yanjun Zhou9Jun Li10Guowei Fu11Yiheng Zhou12Pengwei Sun13Jing Bai14Xuefeng Xia15Xin Yi16Ling Yang17Chaoqun Chen18Junnan Tang19Ang Li20Zujiang Yu21Department of Extracorporeal Life Support Center, Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou UniversityGeneplus-Beijing Institute, 9th Floor, No.6 Building, Peking University Medical Industrial Park, Zhongguancun Life Science ParkGeneplus-Beijing Institute, 9th Floor, No.6 Building, Peking University Medical Industrial Park, Zhongguancun Life Science ParkGene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou UniversityGene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Extracorporeal Life Support Center, Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Extracorporeal Life Support Center, Department of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou UniversityHenan Medical School of Zhengzhou UniversityDepartment of Cardiac Surgery, The First Affiliated Hospital of Zhengzhou UniversityGeneplus-Beijing Institute, 9th Floor, No.6 Building, Peking University Medical Industrial Park, Zhongguancun Life Science ParkGene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou UniversityGeneplus-Beijing Institute, 9th Floor, No.6 Building, Peking University Medical Industrial Park, Zhongguancun Life Science ParkGeneplus-Beijing Institute, 9th Floor, No.6 Building, Peking University Medical Industrial Park, Zhongguancun Life Science ParkOrgan Procurement Organizations, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Cardiology, The First Affiliated Hospital of Zhengzhou UniversityGene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou UniversityGene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou UniversityAbstract Myocarditis is inflammatory injury of the myocardium and causes approximately 30,000 deaths globally each year. Fulminant myocarditis is an extremely severe form of myocarditis. Currently, the clinical evaluation of myocarditis and fulminant myocarditis is primarily based on symptoms, ECG findings, and biochemical markers. Cardiac magnetic resonance and endomyocardial biopsy can provide further support for the diagnosis, but both have limitations in routine practice. Recent studies have shown that cell-free DNA (cfDNA) has distinct methylation patterns depending on the organ of origin, suggesting new possibilities for tracking specific types of organ damage. The core mechanism of fulminant myocarditis is a cytokine storm, leading to multiorgan damage, differing from clinically suspected myocarditis. We performed Genome-wide cfDNA methylation detection on plasma from 20 healthy donors and 22 patients (fulminant myocarditis: clinically suspected myocarditis = 9:13, COVID-19 positive: COVID-19 negative = 14:8) and found that cfDNA can be used to specifically identify early multiorgan damage caused by fulminant myocarditis, and its AUC is superior to traditional biochemical indicators such as troponin, high-sensitivity troponin, and lactate dehydrogenase. This is critically important for the timely clinical recognition and treatment of this condition. Furthermore, our study findings suggest that SARS-CoV-2 infection may exacerbate the severity of myocarditis and multiorgan damage. In summary, cfDNA shows great potential as a noninvasive, early, and sensitive biomarker for reflecting disease severity and systemic injury in fulminant myocarditis, which may help guide earlier risk stratification and intervention.https://doi.org/10.1186/s13148-025-01914-zCell-free DNAFulminant myocarditisMultiorgan damageEarly identificationCytokine storm
spellingShingle Yangchao Zhao
Yujia Wang
Xi Zhao
Xin Zhang
Haoyan Wang
Liang Cui
Huifen Wang
Weiwei Zhu
Boyan Li
Yanjun Zhou
Jun Li
Guowei Fu
Yiheng Zhou
Pengwei Sun
Jing Bai
Xuefeng Xia
Xin Yi
Ling Yang
Chaoqun Chen
Junnan Tang
Ang Li
Zujiang Yu
cfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients
Clinical Epigenetics
Cell-free DNA
Fulminant myocarditis
Multiorgan damage
Early identification
Cytokine storm
title cfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients
title_full cfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients
title_fullStr cfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients
title_full_unstemmed cfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients
title_short cfDNA methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients
title_sort cfdna methylation detection as potential liquid biopsy of multiple organ injury in myocarditis patients
topic Cell-free DNA
Fulminant myocarditis
Multiorgan damage
Early identification
Cytokine storm
url https://doi.org/10.1186/s13148-025-01914-z
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