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CpG-island methylation study of liver fluke-related cholangiocarcinoma

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Title: CpG-island methylation study of liver fluke-related cholangiocarcinoma
Authors: Sriraksa, R
Zeller, C
El-Bahrawy, MA
Dai, W
Daduang, J
Jearanaikoon, P
Chau-in, S
Brown, R
Limpaiboon, T
Item Type: Journal Article
Abstract: Background: Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers. Methods: We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry. Results: A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1. Conclusion: Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP.
Issue Date: 12-Apr-2011
Date of Acceptance: 1-Mar-2011
URI: http://hdl.handle.net/10044/1/65117
DOI: https://dx.doi.org/10.1038/bjc.2011.102
ISSN: 0007-0920
Publisher: Springer Nature
Start Page: 1313
End Page: 1318
Journal / Book Title: British Journal of Cancer
Volume: 104
Issue: 8
Copyright Statement: © 2011 Cancer Research UK. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
Sponsor/Funder: Cancer Research UK
Funder's Grant Number: 13086
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
DNA methylation
cholangiocarcinoma
liver fluke
OPCML
DcR1
biomarkers
TUMOR-SUPPRESSOR GENES
SYRIAN GOLDEN-HAMSTERS
OPISTHORCHIS-VIVERRINI
PROMOTER METHYLATION
P53 PROTEIN
INTRAHEPATIC CHOLANGIOCARCINOMA
EPIGENETIC INACTIVATION
NORTHEAST THAILAND
OVARIAN-CANCER
BREAST-CANCER
Aged
Animals
Bile Duct Neoplasms
Bile Ducts, Intrahepatic
Case-Control Studies
Cholangiocarcinoma
CpG Islands
DNA Methylation
Epigenomics
Fasciola hepatica
Fascioliasis
Female
Humans
Male
Middle Aged
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Online Publication Date: 2011-03-29
Appears in Collections:Division of Surgery
Division of Cancer
Department of Medicine
Faculty of Medicine



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