A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma

Molecular Cancer

Correspondence

Woojin Kim¹  Hyunsoo Kim²  Jin-Young Lee³  Jiwon Kim⁴  Jeongsil Kim-Ha⁴  Chaesun Kwon⁴  Jung-Hwan Yoon⁵  Eun Ju Cho⁵  Su Jong Yu⁵  Yoon Jun Kim⁵  Won Kim⁶  Suk Kyun Hong⁷  YoungRok Choi⁷  Nam-Joon Yi⁷  Kwang-Woong Lee⁷  Kyung-Suk Suh⁷  Young-Joon Kim⁸  Da-Won Kim⁹  Si-Cho Kim⁹ 

[1] Department of Bio-AI convergence, Chungnam National University, Daejeon, Republic of Korea;Department of Bio-AI convergence, Chungnam National University, Daejeon, Republic of Korea;Department of Convergent Bioscience and Informatics, Chungnam National University, Daejeon, Republic of Korea;Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 03722, Seoul, Republic of Korea;Department of Integrative Bioscience & Biotechnology, College of Life Sciences, Sejong University, Seoul, Republic of Korea;Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 03080, Seoul, Republic of Korea;Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Republic of Korea;Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea;Interdisciplinary Program of Integrated OMICS for Biomedical Science, Yonsei University, Seoul, Republic of Korea;Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, 03722, Seoul, Republic of Korea;Interdisciplinary Program of Integrated OMICS for Biomedical Science, Yonsei University, Seoul, Republic of Korea;R&D center, LepiDyne Inc, Seoul, Republic of Korea;

关键词: Hepatocellular carcinoma;    Methylation-sensitive high-resolution melting analysis;    Liquid biopsy;    Cell-free DNA;    Biomarker;    Cancer diagnosis;    DNA methylation.;   

DOI  :  10.1186/s12943-023-01872-1

 received in 2023-06-27, accepted in 2023-09-26,  发布年份 2023

来源: Springer

【 摘 要 】

To address the shortcomings of current hepatocellular carcinoma (HCC) surveillance tests, we set out to find HCC-specific methylation markers and develop a highly sensitive polymerase chain reaction (PCR)-based method to detect them in circulating cell-free DNA (cfDNA). The analysis of large methylome data revealed that Ring Finger Protein 135 (RNF135) and Lactate Dehydrogenase B (LDHB) are universally applicable HCC methylation markers with no discernible methylation level detected in any other tissue types. These markers were used to develop Methylation Sensitive High-Resolution Analysis (MS-HRM), and their diagnostic accuracy was tested using cfDNA from healthy, at-risk, and HCC patients. The combined MS-HRM RNF135 and LDHB analysis detected 57% of HCC, outperforming the alpha-fetoprotein (AFP) test’s sensitivity of 45% at comparable specificity. Furthermore, when used with the AFP test, the methylation assay can detect 70% of HCC. Our findings suggest that the cfDNA methylation assay could be used for HCC liquid biopsy.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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