Correspondence to editorial on “Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma”

Article information

Clin Mol Hepatol. 2025;31(2):e206-e207

Publication date (electronic) : 2025 February 17

doi : https://doi.org/10.3350/cmh.2025.0164

Kwang-Woong Lee^1,2, Young-Joon Kim^,3,4

¹Department of Surgery, Seoul National University Hospital, Seoul, Korea

²Department of Surgery, Seoul National University College of Medicine, Seoul, Korea

³R&D center, LepiDyne Inc., Seoul, Korea

⁴Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea

Corresponding author : Young-Joon Kim Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea Tel: +82-2-2123-2628, Fax: +82-2-2138-3828, E-mail: yjkim@yonsei.ac.kr

Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea

Received 2025 February 11; Accepted 2025 February 14.

Dear Editor,

We sincerely appreciate the insightful editorial by Huang et al. regarding our recent study, “Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma” [1]. Their thoughtful discussion highlights key aspects of our work and further contextualizes the role of DNA methylation markers in predicting hepatocellular carcinoma (HCC) recurrence. We take this opportunity to address some key points raised in their editorial and provide additional insights into our findings.

As noted in the editorial, DNA methylation is a critical epigenetic mechanism influencing tumor biology, including recurrence risk [2,3]. Our study identified a panel of methylation markers with strong predictive power for de novo recurrence, achieving high sensitivity (95.5%), specificity (89.7%), and overall accuracy (92.2%). These results reinforce the growing recognition of methylation-based biomarkers in prognostic modeling for HCC recurrence.

The editorial discusses the robustness of DNA methylation markers across different sample types and preservation methods. Our findings support this view, demonstrating that these signatures remain stable in both fresh-frozen and archival samples. This characteristic makes them particularly attractive for clinical translation, enabling retrospective analyses and broad applicability in diverse clinical settings including optimal indication of the preemptive liver transplantation [4,5].

As pointed out by Huang et al., an effective prognostic model often combines molecular markers with clinical variables [6]. Our study incorporated methylation signatures into a machine learning framework, showing that patients classified as high risk by our model had significantly worse recurrence-free survival. These findings align with prior studies demonstrating the prognostic value of integrating epigenetic and clinical factors [7].

The editorial raises an important question regarding the potential for methylation markers to guide personalized treatment strategies, including immunotherapy. Emerging evidence suggests that methylation status may correlate with immune evasion and response to immunotherapy [8,9]. Further studies are needed to explore whether patients identified as high-risk by our model may benefit from intensified post-surgical surveillance or adjuvant therapies.

We appreciate the editorial’s comprehensive analysis of our work and its broader implications. As interest in methylation-based biomarkers grows, we anticipate that the integration of these signatures into clinical practice could enhance precision in HCC management. We look forward to further collaborations and validation studies to optimize their clinical application.