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Methylation-sensitive high-resolution melting analysis of the USP44 promoter can detect early-stage hepatocellular carcinoma in blood samples

  • Si-Cho, Kim (Interdisciplinary Program of Integrated OMICS for Biomedical Science, Yonsei University) ;
  • Jiwon, Kim (Department of Integrative Bioscience & Biotechnology, College of Life Sciences, Sejong University) ;
  • Da-Won, Kim (Interdisciplinary Program of Integrated OMICS for Biomedical Science, Yonsei University) ;
  • Yanghee, Choi (Department of Integrative Bioscience & Biotechnology, College of Life Sciences, Sejong University) ;
  • Kyunghyun, Park (Department of Integrative Bioscience & Biotechnology, College of Life Sciences, Sejong University) ;
  • Eun Ju, Cho (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Su Jong, Yu (Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine) ;
  • Jeongsil, Kim-Ha (Department of Integrative Bioscience & Biotechnology, College of Life Sciences, Sejong University) ;
  • Young-Joon, Kim (Interdisciplinary Program of Integrated OMICS for Biomedical Science, Yonsei University)
  • Received : 2022.07.13
  • Accepted : 2022.08.01
  • Published : 2022.11.30

Abstract

Hepatocellular carcinoma (HCC) is dangerous cancer that often evades early detection because it is asymptomatic and an effective detection method is lacking. For people with chronic liver inflammation who are at high risk of developing HCC, a sensitive detection method for HCC is needed. In a meta-analysis of The Cancer Genome Atlas pan-cancer methylation database, we identified a CpG island in the USP44 promoter that is methylated specifically in HCC. We developed methylation-sensitive high-resolution melting (MS-HRM) analysis to measure the methylation levels of the USP promoter in cell-free DNA isolated from patients. Our MS-HRM assay correctly identified 40% of patients with early-stage HCC, whereas the α-fetoprotein test, which is currently used to detect HCC, correctly identified only 25% of early-stage HCC patients. These results demonstrate that USP44 MS-HRM analysis is suitable for HCC surveillance.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Ministry of Science & ICT (grant number: 2017M3A9A7050614).

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