Loci-specific differences in blood DNA methylation in HBV-negative populations at risk for hepatocellular carcinoma development
File(s)Lubecka et al accepted 173361_0_merged_1476798381.pdf (2.27 MB)
Accepted version
Author(s)
Type
Journal Article
Abstract
Late onset of clinical symptoms in hepatocellular carcinoma (HCC) results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable tools that would distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed. We used the Illumina HumanMethylation450 BeadChip microarray to test whether white blood cell DNA, an easily accessible source of DNA, exhibits site-specific changes in DNA methylation in blood of diagnosed HCC patients (post-diagnostic, 24 cases, 24 controls) and in prospectively collected blood specimens of HCC patients who were cancer-free at blood collection (pre-diagnostic, 21 cases, 21 controls). Out of 22 differentially methylated loci selected for validation by pyrosequencing, 19 loci with neighbouring CpG sites (probes) were confirmed in the pre-diagnostic study group and subjected to verification in a prospective cirrhotic cohort (13 cases, 23 controls). We established for the first time 9 probes that could distinguish HBV-negative cirrhotic patients who subsequently developed HCC from those who stayed cancer-free. These probes were identified within regulatory regions of BARD1, MAGEB3, BRUNOL5, FXYD6, TET1, TSPAN5, DPPA5, KIAA1210, and LSP1. Methylation levels within DPPA5, KIAA1210, and LSP1 were higher in prospective samples from HCC cases versus cirrhotic controls. The remaining probes were hypomethylated in cases compared with controls. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established probes have potential to be developed into a routine clinical test after validation in larger cohorts.
Date Issued
2018-07-30
Date Acceptance
2018-05-15
ISSN
1559-2294
Publisher
Taylor & Francis
Start Page
605
End Page
626
Journal / Book Title
Epigenetics
Volume
13
Issue
6
Copyright Statement
© 2018 Informa UK Limited, trading as Taylor & Francis Group. This is an Accepted Manuscript of an article published by Taylor & Francis in Epigenetics on 21 Jun 2018, available online: https://www.tandfonline.com/doi/pdf/10.1080/15592294.2018.1481706
Source Database
manual-entry
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29927686
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Genetics & Heredity
DNA methylation
HCC
early detection
cirrhotic populations
LIVER-CANCER
GENOME-WIDE
COLORECTAL-CANCER
MONONUCLEAR-CELLS
PROSTATE-CANCER
LEUKOCYTE DNA
HYPOMETHYLATION
GENES
PROTEIN
BREAST
DNA methylation
HCC
cirrhotic populations
early detection
Biomarkers, Tumor
Carcinoma, Hepatocellular
DNA Methylation
Female
Genetic Loci
Genetic Predisposition to Disease
Humans
Liver Neoplasms
Male
Humans
Carcinoma, Hepatocellular
Liver Neoplasms
Genetic Predisposition to Disease
DNA Methylation
Female
Male
Genetic Loci
Biomarkers, Tumor
DNA methylation
HCC
cirrhotic populations
early detection
0604 Genetics
0601 Biochemistry and Cell Biology
1101 Medical Biochemistry and Metabolomics
Developmental Biology
Publication Status
Published
Country
United States
Date Publish Online
2018-06-21