Plasma cell free DNA methylation markers for hepatocellular carcinoma surveillance in patients with cirrhosis: a case control study

BMC Gastroenterology

Edward Mena¹  Jorge Garces²  Gunter Weiss²  Johanna Aoyama²  Stefanie Kasielke²  Oliver Hasinger²  Denise Kottwitz²  Florian Knaust²  Sebastian Rausch²  Jörn Lewin²  Preeti Rathi²  Theo deVos³  Tse-Ling Fong⁴  Alexander Zipprich⁵ 

[1] California Liver Research Institute, 301 S. Fair Oaks Avenue, Suite 409, 91105, Pasadena, CA, USA;Epigenomics AG, Geneststr. 5, 10829, Berlin, Germany;Epigenomics Inc., 11055 Flintkote Ave, Suite A, 92121, San Diego, CA, USA;Keck School of Medicine, USC, 1510 San Pablo Street, 2/F, 90033, Los Angeles, CA, USA;Universitätsklinik und Poliklinik für Innere Medizin I, UKH Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany;

关键词: Carcinoma;    Hepatocellular;    Liver cirrhosis;    Early detection of cancer;    Biomarker;    Cell-free nucleic acids;    DNA methylation;   

DOI  :  10.1186/s12876-021-01714-8

来源: Springer

【 摘 要 】

BackgroundHepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis, primarily due to failed early detection. HCC screening is recommended among individuals with cirrhosis using biannual abdominal ultrasound, for earlier tumor detection, administration of curative treatment, and improved survival. Surveillance by imaging with or without biomarkers such as alpha-fetoprotein (AFP) remains suboptimal for early stage HCC detection. Here we report on the development and assessment of methylation biomarkers from liquid biopsies for HCC surveillance in cirrhotic patients.MethodsDNA methylation markers including the HCCBloodTest (Epigenomics AG) and a DNA-methylation panel established by next generation sequencing (NGS) were assessed using a training/testing design. The NGS panel algorithm was established in a training study (41 HCC patients; 46 cirrhotic non-HCC controls). For testing, plasma samples were obtained from cirrhotic patients (Child class A or B) with (60) or without (103) early stage HCC (BCLC stage 0, A, B). The assays were then tested using blinded sample sets and analyzed by preset algorithms.ResultsThe HCCBloodTest and the NGS panel exhibited 76.7% and 57% sensitivities at 64.1% and 97% specificity, respectively. In a post-hoc analysis, a combination of the NGS panel with AFP (20 ng/mL) achieved 68% sensitivity at 97% specificity (AUC = 0.9).ConclusionsMethylation biomarkers in cell free plasma DNA provide a new alternative for HCC surveillance. Multiomic panels comprising DNA methylation markers with other biological markers, such as AFP, provide an option to further increase the overall clinical performance of surveillance via minimally invasive blood samples.Trial Registration: Test set study—ClinicalTrials.gov (NCT03804593) January 11, 2019, retrospectively registered.

【 授权许可】

CC BY