Altered Expression of Oxidative Metabolism Related Genes in Cholangiocarcinomas

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.

Identification of a 5-gene-based signature to predict prognosis and correlate immunomodulators for rectal cancer

“…The HGD gene encodes one of the enzymes called homogentisate 1,2 dioxygenase, which is required for the catabolism of the amino acids tyrosine and phenylalanine and is generally active in the kidneys and liver to catalyze oxidation-reduction reactions. The current study showed that high HGD mRNA expression (≥ 3-fold) was associated with poorer survival of, histological grade, advanced stage, and metastasis of cholangiocarcinoma patients [29]. Previous results have shown that HGD is a potential key factor in the regulatory mechanism of BRAFV600E-mediated PTC.…”

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“…In addition, EIF5A2 regulates the resistance of gastric cancer cells to cisplatin by mediating epithelial-stromal transformation (Sun et al, 2018). The downregulation of HGD expression was found to be associated with less metastasis, as well as better prognosis, pathological grade, and clinical stage of cholangiocarcinoma patients (Aukkanimart et al, 2015). The PLS1 was overexpressed in CRC patients and associated with lymph node metastasis and a poor prognosis.…”