Loci-specific differences in blood DNA methylation in HBV-negative populations at risk for hepatocellular carcinoma development

Autor: Lucinda Kurzava, Suthat Liangpunsakul, Katarzyna Lubecka, George P. McCabe, Naga Chalasani, Megan Beetch, Barbara Stefanska, Samer Gawrieh, Adam Ruhayel, Kirsty Flower, Hannah Buvala, James M. Flanagan, Jay Qiu, Tracy Gonzalez
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Cancer Research
Cirrhosis
Microarray
Colorectal cancer
HYPOMETHYLATION
PROTEIN
0601 Biochemistry and Cell Biology
Gastroenterology
COLORECTAL-CANCER
LIVER-CANCER
HCC
early detection
Genetics & Heredity
Liver Neoplasms
PROSTATE-CANCER
LEUKOCYTE DNA
medicine.anatomical_structure
1101 Medical Biochemistry and Metabolomics
Hepatocellular carcinoma
DNA methylation
Female
Liver cancer
Life Sciences & Biomedicine
Research Paper
medicine.medical_specialty
Biochemistry & Molecular Biology
GENES
Carcinoma
Hepatocellular
Biology
BREAST
03 medical and health sciences
Internal medicine
White blood cell
medicine
Biomarkers
Tumor
Humans
Genetic Predisposition to Disease
Molecular Biology
MONONUCLEAR-CELLS
0604 Genetics
Science & Technology
GENOME-WIDE
Cancer
DNA Methylation
medicine.disease
030104 developmental biology
Genetic Loci
cirrhotic populations
Developmental Biology
Zdroj: Epigenetics. 13(6)
ISSN: 1559-2308
Popis: 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.
Databáze: OpenAIRE
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