title: CpG-island methylation study of liver fluke-related cholangiocarcinoma.
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.
  
  
  CONCLUSIONS
  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.
authors: Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand.
authors: R
authors: R
authors: Sriraksa
authors: C
authors: C
authors: Zeller
authors: M A
authors: MA
authors: El-Bahrawy
authors: W
authors: W
authors: Dai
authors: J
authors: J
authors: Daduang
authors: P
authors: P
authors: Jearanaikoon
authors: S
authors: S
authors: Chau-In
authors: R
authors: R
authors: Brown
authors: T
authors: T
authors: Limpaiboon
mesh_terms: D000368:Aged; D000818:Animals; D001650:Bile Duct Neoplasms / Q000209:etiology* / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic / Q000473:pathology; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000209:etiology* / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D057890:Epigenomics; D005210:Fasciola hepatica / Q000502:physiology; D005211:Fascioliasis / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged