ArticleMicrobiology spectrum2025
TUBB1 promoter methylation is a promising biomarker for predicting HBeAg seroconversion in chronic hepatitis B.
Article in Microbiology spectrum, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Early on-treatment dynamics predicting hepatitis B e antigen seroconversion in chronic hepatitis B.Frontiers in immunology · 2026Article
- Altered expression of MX2 and SAMD4A in PBMCs predicts early treatment responses in HBeAg-positive chronic hepatitis B patients during Peg-IFN-α therapy.Frontiers in pharmacology · 2026Article
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8 authors.
Funding
Abstract
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, 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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