Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2010-10-4
pubmed:abstractText
Transcriptional silencing of tumor suppressor genes and other cancer-related genes induced by promoter CpG island hypermethylation is an important epigenetic mechanism of hepatocarcinogenesis. Previous studies have established methylation profiles of hepatocellular carcinomas (HCCs) and demonstrated that methylation of several candidate genes in resected tissues may be associated with time to recurrence. The goals of our study were to test whether specific promoter methylation and mRNA levels of candidate genes, as well as global changes in DNA methylation, can be linked with time to recurrence and clinicopathological variables in a homogenous study group of HCC patients. Forty-three tumorous and 45 non-tumorous liver tissue samples from the surgical margin were obtained from HCV-positive, HBV-negative HCC patients who underwent tumor resection surgery and who were monitored for tumor recurrence thereafter (median follow-up time: 16 months (range, 0-79 months)). Methylation-specific PCR was used to assess the promoter methylation status of P16(INK4a), SOCS-1, RASSF1A, APC, GSTP1, RIZ1, and MGMT genes, while the level of LINE-1 methylation was used as marker of global DNA methylation levels. Methylation frequencies in P16(INK4a), RASSF1A, APC, GSTP1, and RIZ1 genes were significantly greater in tumorous versus non-tumorous tissues. Methylation of RIZ1 in non-tumorous tissues was significantly associated with time to recurrence. Additionally, genomic DNA was significantly more hypomethylated in tumorous tissues, and this change was associated with shorter recurrence, but not with clinicopathological features. In conclusion, this study supports the role of aberrant methylation in the pathobiology of HCV-positive HCCs. The finding that RIZ1 methylation and increased levels of LINE-1 hypomethylation in non-tumorous tissues are associated with time to recurrence underscores the importance of assessing the epigenetic state of the liver remnant.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0027-5107
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
692
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
26-33
pubmed:dateRevised
2011-10-13
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Comparative analysis of promoter methylation and gene expression endpoints between tumorous and non-tumorous tissues from HCV-positive patients with hepatocellular carcinoma.
pubmed:affiliation
Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural