Altered Expression of Oxidative Metabolism Related Genes in Cholangiocarcinomas

Cholangiocarcinoma (CCA) is a rare but highly fatal cancer for which the molecular mechanisms anddiagnostic 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 tumorigenesisof O. viverrini infection-associated CCA in an animal model, and confirmed down-regulation of expression inhuman cases of opisthorchiasis-associated CCA through real time PCR. Kinetic expression of HGD, IDH1 andIDH2 in the animal model of O. viverrini infection-induced CCA was correlated with human CCA cases. In theanimal model, expression of HGD was decreased at all time points (p<0.01) and expression of both IDH1 andIDH2 was decreased in the CCA group. In human cases, expression of HGD, IDH1 and IDH2 was decreasedmore than 2 fold in 55 cases (70.5%), 25 cases (32.1%) and 24 cases (30.8%) respectively. The present studysuggests that reduction of HGD, IDH1 and IDH2 may be involve in cholangiocarcinoma genesis and may beuseful for molecular diagnosis.