Abstract
Cholangiocarcinoma (CCA) is a rare but highly fatal cancer for which the molecular mechanisms and diagnostic markers are obscure. We therefore investigated the kinetic expression of isocitrate dehydrogenase-1 (IDH1), isocitrate dehydrogenase-2 (IDH2) and homogentisate 1,2-dioxygenase (HGD) during the tumorigenesis of O. viverrini infection-associated CCA in an animal model, and confirmed down-regulation of expression in human cases of opisthorchiasis-associated CCA through real time PCR. Kinetic expression of HGD, IDH1 and IDH2 in the animal model of O. viverrini infection-induced CCA was correlated with human CCA cases. In the animal model, expression of HGD was decreased at all time points (p<0.01) and expression of both IDH1 and IDH2 was decreased in the CCA group. In human cases, expression of HGD, IDH1 and IDH2 was decreased more than 2 fold in 55 cases (70.5%), 25 cases (32.1%) and 24 cases (30.8%) respectively. The present study suggests that reduction of HGD, IDH1 and IDH2 may be involve in cholangiocarcinoma genesis and may be useful for molecular diagnosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / genetics
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Adenocarcinoma / metabolism
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Adenocarcinoma / mortality
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Adenocarcinoma / secondary
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Animals
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Bile Duct Neoplasms / genetics
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Bile Duct Neoplasms / metabolism*
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Bile Duct Neoplasms / mortality
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Bile Duct Neoplasms / pathology
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Bile Ducts, Intrahepatic / metabolism*
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Bile Ducts, Intrahepatic / pathology
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Carcinoma, Papillary / genetics
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Carcinoma, Papillary / metabolism
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Carcinoma, Papillary / mortality
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Carcinoma, Papillary / secondary
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Cell Transformation, Neoplastic / metabolism*
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Cell Transformation, Neoplastic / pathology
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Cholangiocarcinoma / genetics
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Cholangiocarcinoma / metabolism*
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Cholangiocarcinoma / mortality
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Cholangiocarcinoma / pathology
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Disease Models, Animal
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Down-Regulation
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Female
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Follow-Up Studies
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Homogentisate 1,2-Dioxygenase / metabolism*
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Humans
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Isocitrate Dehydrogenase / metabolism*
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Male
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Mesocricetus
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Middle Aged
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Neoplasm Staging
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Opisthorchiasis / metabolism
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Opisthorchiasis / mortality
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Opisthorchiasis / parasitology
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Opisthorchiasis / pathology
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Opisthorchis / physiology
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Prognosis
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Real-Time Polymerase Chain Reaction
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Survival Rate
Substances
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Isocitrate Dehydrogenase
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Homogentisate 1,2-Dioxygenase