Zhu Hanxu, Zhang Feng, Tian Zhezhe, Xu Miaomiao, Fan Yuchen, Gao Shuai, Wang Kai
Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Hepatology Institute of Shandong University, Jinan, Shandong, China.
Front Med (Lausanne). 2025 Aug 8;12:1631990. doi: 10.3389/fmed.2025.1631990. eCollection 2025.
New 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.
The 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.
Patients 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.
Ring 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.
需要新的生物标志物来更早地检测肝硬化并使治疗策略个体化。本研究专门调查了无名指蛋白41启动子甲基化作为一种表观遗传生物标志物在检测早期乙型肝炎病毒相关肝硬化方面的诊断潜力。
采用甲基化荧光定量分析法对190名参与者外周血单个核细胞中无名指蛋白41启动子的甲基化水平进行定量，并同时分析与肝纤维化相关的血清炎症细胞因子的变化。
早期肝硬化患者无名指蛋白41启动子的甲基化水平显著高于慢性乙型肝炎患者和健康对照，且mRNA表达降低。值得注意的是，受试者工作特征分析表明，无名指蛋白41启动子甲基化在区分乙型肝炎病毒相关代偿期肝硬化方面具有卓越的诊断性能（曲线下面积），优于包括肝脏硬度测量、天冬氨酸转氨酶与血小板比值指数和纤维化-4评分在内的传统非侵入性指标。
无名指蛋白41可能在肝硬化发病机制中起关键作用，其在外周血单个核细胞中的甲基化状态显示出作为早期肝硬化检测的非侵入性生物标志物的强大潜力。
