TUBB1启动子甲基化是预测慢性乙型肝炎HBeAg血清转化的一个有前途的生物标志物。

IF 3.8 2区生物学 Q2 MICROBIOLOGY

Microbiology spectrum Pub Date : 2025-10-09 DOI:10.1128/spectrum.01344-25

Tong Zhao, Yuna Tang, Yu Sun, Jihui Li, Yuchen Fan, Chao Cui, Shuai Gao, Kai Wang

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引用次数: 0

摘要

确定慢性乙型肝炎（CHB）患者乙型肝炎e抗原血清转化（HBeAg SC）的预测指标仍然是一个挑战。我们的目的是研究外周血单核细胞（PBMCs）中TUBB1启动子甲基化是否可以预测HBeAg SC，共招募了271名参与者，其中包括145名HBeAg阳性CHB患者，94名HBeAg阴性CHB患者和32名健康对照（hc）。hbeag阳性CHB患者随访72周。分别使用MethyLight和实时荧光定量PCR检测PBMCs中TUBB1启动子甲基化和相应mRNA水平。与HBeAg和hc阴性患者相比，HBeAg阳性患者的TUBB1启动子甲基化水平显著升高。相反，与HBeAg和hc阴性患者相比，HBeAg阳性患者中TUBB1的相对mRNA表达水平显著下调。TUBB1启动子甲基化水平在CHB的四个阶段逐渐降低。HBeAg SC患者的TUBB1启动子甲基化基线水平低于未患HBeAg SC的患者，TUBB1启动子甲基化是HBeAg SC的独立预测因子（优势比[OR] = 0.683, 95% CI 0.553-0.845, P < 0.001）。TUBB1启动子甲基化对HBeAg阳性患者的HBeAg SC具有良好的预测价值（曲线下面积[AUC] = 0.805, 95% CI 0.704-0.907, P < 0.001）。TUBB1启动子的甲基化水平可能是预测HBeAg SC的有效生物标志物。重要性：先前的研究强调乙型肝炎e抗原血清转化（HBeAg SC）是慢性乙型肝炎（CHB）缓解与疾病进展风险降低相关的里程碑。虽然HBeAg SC的重要性得到广泛认可，但实现这一终点的可靠的非侵入性预测指标仍然有限。此外，在我们之前的研究中，关键调控基因的DNA甲基化与慢性乙型肝炎的进展有关。然而，TUBB1启动子甲基化与HBeAg SC之间的关系及其作为临床应用生物标志物的潜力尚未完全阐明。我们证明，在HBeAg阳性患者中，TUBB1启动子甲基化水平显著较高，并且在72周的随访期间，甲基化水平降低与随后的HBeAg SC独立相关。我们的研究结果强调了TUBB1启动子甲基化作为预测HBeAg SC的非侵入性生物标志物的潜在临床应用。本研究提供了强有力的证据支持TUBB1启动子甲基化在预测HBeAg SC中的作用，为监测CHB提供了一种新的生物标志物。

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TUBB1 promoter methylation is a promising biomarker for predicting HBeAg seroconversion in chronic hepatitis B.

The identification of predictive indices for hepatitis B e antigen seroconversion (HBeAg SC) in patients with chronic hepatitis B (CHB) remains a challenge. We aimed to investigate whether the TUBB1 promoter methylation in peripheral blood mononuclear cells (PBMCs) can predict HBeAg SC. A total of 271 participants were recruited, comprising 145 patients with HBeAg-positive CHB, 94 with HBeAg-negative CHB, and 32 healthy controls (HCs). The patients with HBeAg-positive CHB were followed up for 72 weeks. The TUBB1 promoter methylation and the corresponding mRNA levels in PBMCs were detected using MethyLight and quantitative real-time PCR, respectively. The methylation levels of the TUBB1 promoter were remarkably elevated in patients with positive HBeAg, in comparison to those with negative HBeAg and HCs. Conversely, the relative mRNA expression levels of TUBB1 were significantly downregulated in patients with positive HBeAg, when compared to those with negative HBeAg and HCs. The TUBB1 promoter methylation levels showed a gradual decrease across the four phases of CHB. Patients with HBeAg SC had lower baseline methylation levels of the TUBB1 promoter than those without HBeAg SC. The TUBB1 promoter methylation was an independent predictor of HBeAg SC (odds ratio [OR] = 0.683, 95% CI 0.553-0.845, P < 0.001). The methylation of the TUBB1 promoter showed good predictive value for HBeAg SC in patients with positive HBeAg (area under the curve [AUC] = 0.805, 95% CI 0.704-0.907, P < 0.001). The methylation level of the TUBB1 promoter might be a potent biomarker for predicting HBeAg SC.

Importance: Previous studies emphasized hepatitis B e antigen seroconversion (HBeAg SC) as a milestone for chronic hepatitis B (CHB) remission associated with reduced disease progression risks. While the significance of HBeAg SC is widely recognized, reliable non-invasive predictors for achieving this endpoint remain limited. Additionally, in our previous studies, DNA methylation of key regulatory genes has been linked to CHB progression. However, the association between TUBB1 promoter methylation and HBeAg SC, as well as its potential as a biomarker for clinical application, has not been fully elucidated. We demonstrated that TUBB1 promoter methylation levels were significantly higher in HBeAg-positive patients and that decreased methylation levels were independently associated with subsequent HBeAg SC during a 72-week follow-up. Our findings underscore the potential clinical utility of TUBB1 promoter methylation as a non-invasive biomarker for predicting HBeAg SC. This study provides strong evidence supporting the role of TUBB1 promoter methylation in predicting HBeAg SC, offering a novel biomarker for monitoring CHB.

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来源期刊

Microbiology spectrum Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.20

自引率

5.40%

发文量

1800

期刊介绍： Microbiology Spectrum publishes commissioned review articles on topics in microbiology representing ten content areas: Archaea; Food Microbiology; Bacterial Genetics, Cell Biology, and Physiology; Clinical Microbiology; Environmental Microbiology and Ecology; Eukaryotic Microbes; Genomics, Computational, and Synthetic Microbiology; Immunology; Pathogenesis; and Virology. Reviews are interrelated, with each review linking to other related content. A large board of Microbiology Spectrum editors aids in the development of topics for potential reviews and in the identification of an editor, or editors, who shepherd each collection.