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New advances in hepatocellular carcinoma

World Journal of Hepatology 2016年第9期8卷 421-438页

作者： Sonia Pascual Iván Herrera Javier Irurzun Liver Unit Gastroenterology Department Interventional Radiological Unit Hospital General Universitario de Alicante03010 AlicanteSpain

AIM: To determine if gene-specific dna methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma(HCC).METHODS: Comparing genome-wide dna methylation profiles using Illumina Human methylation 450 K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of dnamethylation patterns observed in tumor tissues can be detected in white blood cell(WBC) dna, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in dna methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC dna from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina Bead Array. We used the χ2 test for categorical variables and student's t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios(OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91(95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1 L, however, were associated with decreased risk. The ORs(95%CI) were 0.59(0.39-0.87) and 0.50(0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC dna as biomarke

关键词： dna methylation Epigenetics Hepatitis B virus Hepatocellular carcinoma white blood cell dna

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