Plasma cell free DNA methylation markers for hepatocellular carcinoma surveillance in patients with cirrhosis: a case control study.
Biomarker
Carcinoma
Cell-free nucleic acids
DNA methylation
Early detection of cancer
Hepatocellular
Liver cirrhosis
Journal
BMC gastroenterology
ISSN: 1471-230X
Titre abrégé: BMC Gastroenterol
Pays: England
ID NLM: 100968547
Informations de publication
Date de publication:
25 Mar 2021
25 Mar 2021
Historique:
received:
24
09
2020
accepted:
09
03
2021
entrez:
26
3
2021
pubmed:
27
3
2021
medline:
15
5
2021
Statut:
epublish
Résumé
Hepatocellular 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. DNA 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. The 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). Methylation 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. Test set study-ClinicalTrials.gov (NCT03804593) January 11, 2019, retrospectively registered.
Sections du résumé
BACKGROUND
BACKGROUND
Hepatocellular 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.
METHODS
METHODS
DNA 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.
RESULTS
RESULTS
The 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).
CONCLUSIONS
CONCLUSIONS
Methylation 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
BACKGROUND
Test set study-ClinicalTrials.gov (NCT03804593) January 11, 2019, retrospectively registered.
Identifiants
pubmed: 33765926
doi: 10.1186/s12876-021-01714-8
pii: 10.1186/s12876-021-01714-8
pmc: PMC7995734
doi:
Substances chimiques
Biomarkers
0
Biomarkers, Tumor
0
Cell-Free Nucleic Acids
0
alpha-Fetoproteins
0
Banques de données
ClinicalTrials.gov
['NCT03804593']
Types de publication
Clinical Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
136Références
Cancer Epidemiol Biomarkers Prev. 2019 Mar;28(3):531-538
pubmed: 30464023
Cancer Epidemiol Biomarkers Prev. 2012 May;21(5):793-9
pubmed: 22374994
Hepatology. 2018 Aug;68(2):723-750
pubmed: 29624699
Cancer Epidemiol Biomarkers Prev. 2014 Jan;23(1):144-53
pubmed: 24220911
Hepatol Commun. 2020 Jan 02;4(3):461-470
pubmed: 32140662
J Pathol. 2004 Nov;204(4):489-505
pubmed: 15495264
Gastroenterology. 2018 May;154(6):1706-1718.e1
pubmed: 29425931
Gut. 2019 Dec;68(12):2195-2205
pubmed: 31358576
EBioMedicine. 2018 Apr;30:138-147
pubmed: 29627389
Oncology. 2021;99(2):114-123
pubmed: 32998139
Bioinformatics. 2011 Nov 1;27(21):2957-63
pubmed: 21903629
Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):E5503-12
pubmed: 26392541
Theranostics. 2019 Sep 25;9(24):7239-7250
pubmed: 31695765
PLoS One. 2008;3(11):e3759
pubmed: 19018278
Int J Biochem Cell Biol. 2007;39(7-8):1539-50
pubmed: 17499000
Nat Commun. 2018 Nov 29;9(1):5068
pubmed: 30498206
Dis Markers. 2017;2017:3726595
pubmed: 29038612
BMC Res Notes. 2019 Aug 30;12(1):551
pubmed: 31470896
Nat Genet. 2006 Dec;38(12):1378-85
pubmed: 17072317
Cancer Epidemiol Biomarkers Prev. 2020 Dec;29(12):2495-2503
pubmed: 32238405
Cancer Metastasis Rev. 2016 Sep;35(3):347-76
pubmed: 27392603