CpG-island methylation study of liver fluke-related cholangiocarcinoma
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. M...
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Veröffentlicht in: | British journal of cancer 2011-04, Vol.104 (8), p.1313-1318 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 0007-0920 1532-1827 |
DOI: | 10.1038/bjc.2011.102 |