PMID- 21448164 OWN - NLM STAT- MEDLINE DCOM- 20110621 LR - 20231115 IS - 1532-1827 (Electronic) IS - 0007-0920 (Print) IS - 0007-0920 (Linking) VI - 104 IP - 8 DP - 2011 Apr 12 TI - CpG-island methylation study of liver fluke-related cholangiocarcinoma. PG - 1313-8 LID - 10.1038/bjc.2011.102 [doi] AB - 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. FAU - Sriraksa, R AU - Sriraksa R AD - Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand. FAU - Zeller, C AU - Zeller C FAU - El-Bahrawy, M A AU - El-Bahrawy MA FAU - Dai, W AU - Dai W FAU - Daduang, J AU - Daduang J FAU - Jearanaikoon, P AU - Jearanaikoon P FAU - Chau-In, S AU - Chau-In S FAU - Brown, R AU - Brown R FAU - Limpaiboon, T AU - Limpaiboon T LA - eng GR - 13086/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110329 PL - England TA - Br J Cancer JT - British journal of cancer JID - 0370635 SB - IM MH - Aged MH - Animals MH - Bile Duct Neoplasms/*etiology/*genetics MH - *Bile Ducts, Intrahepatic/pathology MH - Case-Control Studies MH - Cholangiocarcinoma/*etiology/*genetics MH - CpG Islands/*genetics MH - *DNA Methylation MH - Epigenomics MH - Fasciola hepatica/physiology MH - Fascioliasis/*complications MH - Female MH - Humans MH - Male MH - Middle Aged PMC - PMC3078588 EDAT- 2011/03/31 06:00 MHDA- 2011/06/22 06:00 PMCR- 2012/04/12 CRDT- 2011/03/31 06:00 PHST- 2011/03/31 06:00 [entrez] PHST- 2011/03/31 06:00 [pubmed] PHST- 2011/06/22 06:00 [medline] PHST- 2012/04/12 00:00 [pmc-release] AID - bjc2011102 [pii] AID - 10.1038/bjc.2011.102 [doi] PST - ppublish SO - Br J Cancer. 2011 Apr 12;104(8):1313-8. doi: 10.1038/bjc.2011.102. Epub 2011 Mar 29.