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A circulating cell-free DNA methylation signature for the detection of hepatocellular carcinoma
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- Authors
- Issue Date
- 2023-10-06
- Publisher
- BMC
- Citation
- Molecular Cancer, Vol.22(1):164
- Keywords
- Hepatocellular carcinoma ; Methylation-sensitive high-resolution melting analysis ; Liquid biopsy ; Cell-free DNA ; Biomarker ; Cancer diagnosis ; DNA methylation
- 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) tests 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.
- ISSN
- 1476-4598
- Language
- English
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