Clin Mol Hepatol.
2025 Apr;31(2):563-576. 10.3350/cmh.2024.0899.
Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
- Affiliations
-
- 1Interdisciplinary Program of Integrated OMICS for Biomedical Science, Yonsei University, Seoul, Korea
- 2R&D center, LepiDyne Inc, Seoul, Korea
- 3Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
- 4Department of Surgery, Seoul National University Hospital, Seoul, Korea
- 5Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
- 6Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea
- KMID: 2566976
- DOI: http://doi.org/10.3350/cmh.2024.0899
Abstract
- Background/Aims
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Correspondence to editorial on “Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma”
- Screening of patients at high risk of de novo recurrence in HCC: Editorial on “Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma”
- De novo gastric cancer after liver transplantation: A review of the Asian experience
- De Novo Submucosal Colorectal Cancer in a 3 mm Sessile Polyp
- Comparative Analysis on Methylation Levels of Nerve and Stress Related Genes in Charcot-Marie-Tooth Disease Type 1A Patients
