Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosis

ObjectivesNew biomarkers are needed to detect liver cirrhosis at an earlier stage and to individualize treatment strategies. This study specifically investigates the diagnostic potential of Ring finger protein 41 promoter methylation as an epigenetic biomarker for detecting early-stage hepatitis B v...

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Main Authors: Hanxu Zhu, Feng Zhang, Zhezhe Tian, Miaomiao Xu, Yuchen Fan, Shuai Gao, Kai Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1631990/full
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author Hanxu Zhu
Feng Zhang
Zhezhe Tian
Miaomiao Xu
Yuchen Fan
Yuchen Fan
Shuai Gao
Kai Wang
Kai Wang
author_facet Hanxu Zhu
Feng Zhang
Zhezhe Tian
Miaomiao Xu
Yuchen Fan
Yuchen Fan
Shuai Gao
Kai Wang
Kai Wang
author_sort Hanxu Zhu
collection DOAJ
description ObjectivesNew biomarkers are needed to detect liver cirrhosis at an earlier stage and to individualize treatment strategies. This study specifically investigates the diagnostic potential of Ring finger protein 41 promoter methylation as an epigenetic biomarker for detecting early-stage hepatitis B virus-related liver cirrhosis.MethodsThe methylation level of the Ring finger protein 41 promoter in peripheral blood mononuclear cells of 190 participants were quantified with Methylight, and the changes of serum inflammatory cytokines related to liver fibrosis were analyzed simultaneously.ResultsPatients with early-stage liver cirrhosis exhibited significantly higher methylation levels of Ring finger protein 41 promoter than chronic hepatitis B patients and health controls, accompanied by reduced mRNA expression. Remarkably, the receiver operating characteristic analysis demonstrated that Ring finger protein 41 promoter methylation achieved a superior diagnostic performance (area under the curve) for distinguishing hepatitis B virus-related compensated liver cirrhosis, outperforming conventional non-invasive indicators including liver stiffness measurement, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 score.ConclusionRing finger protein 41 may play a critical role in the pathogenesis of liver cirrhosis, with its methylation status in peripheral blood mononuclear cells demonstrating strong potential as a non-invasive biomarker for early liver cirrhosis detection.
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issn 2296-858X
language English
publishDate 2025-08-01
publisher Frontiers Media S.A.
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series Frontiers in Medicine
spelling doaj-art-a5928e90f8fe4c3785dc4eba00d367372025-08-20T02:55:06ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-08-011210.3389/fmed.2025.16319901631990Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosisHanxu Zhu0Feng Zhang1Zhezhe Tian2Miaomiao Xu3Yuchen Fan4Yuchen Fan5Shuai Gao6Kai Wang7Kai Wang8Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaHepatology Institute of Shandong University, Jinan, Shandong, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaDepartment of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, ChinaHepatology Institute of Shandong University, Jinan, Shandong, ChinaObjectivesNew biomarkers are needed to detect liver cirrhosis at an earlier stage and to individualize treatment strategies. This study specifically investigates the diagnostic potential of Ring finger protein 41 promoter methylation as an epigenetic biomarker for detecting early-stage hepatitis B virus-related liver cirrhosis.MethodsThe methylation level of the Ring finger protein 41 promoter in peripheral blood mononuclear cells of 190 participants were quantified with Methylight, and the changes of serum inflammatory cytokines related to liver fibrosis were analyzed simultaneously.ResultsPatients with early-stage liver cirrhosis exhibited significantly higher methylation levels of Ring finger protein 41 promoter than chronic hepatitis B patients and health controls, accompanied by reduced mRNA expression. Remarkably, the receiver operating characteristic analysis demonstrated that Ring finger protein 41 promoter methylation achieved a superior diagnostic performance (area under the curve) for distinguishing hepatitis B virus-related compensated liver cirrhosis, outperforming conventional non-invasive indicators including liver stiffness measurement, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 score.ConclusionRing finger protein 41 may play a critical role in the pathogenesis of liver cirrhosis, with its methylation status in peripheral blood mononuclear cells demonstrating strong potential as a non-invasive biomarker for early liver cirrhosis detection.https://www.frontiersin.org/articles/10.3389/fmed.2025.1631990/fullRing finger protein 41hepatitis Bliver cirrhosisDNA methylationearly diagnosis
spellingShingle Hanxu Zhu
Feng Zhang
Zhezhe Tian
Miaomiao Xu
Yuchen Fan
Yuchen Fan
Shuai Gao
Kai Wang
Kai Wang
Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosis
Frontiers in Medicine
Ring finger protein 41
hepatitis B
liver cirrhosis
DNA methylation
early diagnosis
title Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosis
title_full Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosis
title_fullStr Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosis
title_full_unstemmed Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosis
title_short Hypermethylation of Ring finger protein 41 promoter is associated with early hepatitis B virus-related cirrhosis
title_sort hypermethylation of ring finger protein 41 promoter is associated with early hepatitis b virus related cirrhosis
topic Ring finger protein 41
hepatitis B
liver cirrhosis
DNA methylation
early diagnosis
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1631990/full
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