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

被引:0
作者
Si-Cho Kim
Da-Won Kim
Eun Ju Cho
Jin-Young Lee
Jiwon Kim
Chaesun Kwon
Jeongsil Kim-Ha
Suk Kyun Hong
YoungRok Choi
Nam-Joon Yi
Kwang-Woong Lee
Kyung-Suk Suh
Won Kim
Woojin Kim
Hyunsoo Kim
Yoon Jun Kim
Jung-Hwan Yoon
Su Jong Yu
Young-Joon Kim
机构
[1] Yonsei University,Interdisciplinary Program of Integrated OMICS for Biomedical Science
[2] LepiDyne Inc,R&D center
[3] Seoul National University College of Medicine,Department of Internal Medicine and Liver Research Institute
[4] Yonsei University,Department of Biochemistry, College of Life Science and Biotechnology
[5] Sejong University,Department of Integrative Bioscience & Biotechnology, College of Life Sciences
[6] Seoul National University College of Medicine,Department of Surgery
[7] Seoul National University College of Medicine,Department of Internal Medicine
[8] Seoul Metropolitan Government Boramae Medical Center,Department of Bio
[9] Chungnam National University,AI convergence
[10] Chungnam National University,Department of Convergent Bioscience and Informatics
来源
Molecular Cancer | / 22卷
关键词
Hepatocellular carcinoma; Methylation-sensitive high-resolution melting analysis; Liquid biopsy; Cell-free DNA; Biomarker; Cancer diagnosis; DNA methylation.;
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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.
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