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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Molecular Cancer, Vol 22, Iss 1, Pp 1-6 (2023)
Druh dokumentu: article
ISSN: 1476-4598
DOI: 10.1186/s12943-023-01872-1
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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