Copyright
©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
Orotate phosphoribosyl transferase mRNA expression and the response of cholangiocarcinoma to 5-fluorouracil
Chariya Hahnvajanawong, Jariya Chaiyagool, Wunchana Seubwai, Vajarabhongsa Bhudhisawasdi, Nisana Namwat, Narong Khuntikeo, Banchob Sripa, Ake Pugkhem, Wichittra Tassaneeyakul
Chariya Hahnvajanawong, Jariya Chaiyagool, Department of Microbiology, Center of Excellence for Innovation in Chemistry, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Wunchana Seubwai, Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Vajarabhongsa Bhudhisawasdi, Narong Khuntikeo, Ake Pugkhem, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Nisana Namwat, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Banchob Sripa, Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Wichittra Tassaneeyakul, Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Author contributions: Tassaneeyakul W and Hahnvajanawong C designed the study, analyzed the data and wrote the paper; Chaiyagool J, Bhudhisawasdi V, Khuntikeo N and Pugkhem A collected the samples; and Hahnvajanawong C, Chaiyagool J, Namwat N, Sripa B and Seubwai W performed the research and analyzed the data.
Supported by The Research Team Strengthening Grant, National Genetic Engineering and Biotechnology Center, National Science and Technology Development Agency, Thailand; The Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Thailand (to Chaiyagool J)
Correspondence to: Chariya Hahnvajanawong, PhD, Assistant Professor, Department of Microbiology, Center of Excellence for Innovation in Chemistry, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. hchari@kku.ac.th
Telephone: +66-43-363808 Fax: +66-43-363808
Received: December 27, 2011
Revised: May 11, 2012
Accepted: May 26, 2012
Published online: August 14, 2012
AIM: To determine whether expression of certain enzymes related to 5-fluorouracil (5-FU) metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma (CCA).
METHODS: The histoculture drug response assay (HDRA) was performed using surgically resected CCA tissues. Tumor cell viability was determined morphologically with hematoxylin and eosin- and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues. The mRNA expression of thymidine phosphorylase (TP), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) was determined with real-time reverse transcriptase-polymerase chain reaction. The levels of gene expression and the sensitivity to 5-FU were evaluated.
RESULTS: Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital, Khon Kaen University from 2007 to 2009. HDRA was used to determine the response of these CCA tissues to 5-FU. Based on the dose-response curve, 200 μg/mL 5-FU was selected as the test concentration. The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU. When the relationship between TP, OPRT, TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined, only OPRT mRNA expression was significantly correlated with the response to 5-FU. The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group (0.41 ± 0.25 vs 0.22 ± 0.12, P < 0.05).
CONCLUSION: OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA. Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.
