Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 14, 2006; 12(26): 4143-4148
Published online Jul 14, 2006. doi: 10.3748/wjg.v12.i26.4143
Amplification of chromosome 21q22.3 harboring trefoil factor family genes in liver fluke related cholangiocarcinoma is associated with poor prognosis
Kanuengnuch Muenphon, Temduang Limpaiboon, Patcharee Jearanaikoon, Chawalit Pairojkul, Banchob Sripa, Vajarabhongsa Bhudhisawasdi
Kanuengnuch Muenphon, Temduang Limpaiboon, Patcharee Jearanaikoon, Department of Clinical Chemistry, Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Chawalit Pairojkul, Banchob Sripa, Department of Pathology, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Vajarabhongsa Bhudhisawasdi, Department of Surgery, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Co-first-author: Temduang Limpaiboon
Supported by the Research Grants from Khon Kaen University, No. 48-03-1-01-03; the Center for Research and Development in Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, No 06-01
Correspondence to: Dr. Temduang Limpaiboon, Department of Clinical Chemistry, Center for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand. temduang@kku.ac.th
Telephone: +66-43-362028 Fax: +66-43-202088
Received: March 14, 2006
Revised: March 20, 2006
Accepted: March 27, 2006
Published online: July 14, 2006
Abstract

AIM: To determine allelic imbalance on chromosomal region 21q22-qter including trefoil factor family genes (TFF) in cholangiocarcinoma (CCA) patients and analyze the correlation between allelic imbalances and clinicopathological parameters.

METHODS: Quantitative PCR amplification was performed on four microsatellite markers and trefoil factor family genes (TFF1, TFF2, and TFF3) using a standard curve and SYBR Green I dye method. The relative copy number was determined by DNA copy number of tested locus to reference locus. The relative copy number was interpreted as deletion or amplification by comparison with normal reference range. Associations between allelic imbalance and clinicopathological parameters of CCA patients were evaluated by χ2-tests. Kaplan-Meier method was used to analyze survival.

RESULTS: The frequencies of amplification at D21S1890, D21S1893, and TFF3 were 32.5%, 30.0%, and 28.7%, respectively. Patients who had amplification at regions covering D21S1893, D21S1890, and TFF showed poor prognosis, whereas patients who had deletion showed favorable prognosis (mean: 51.7 wk vs 124.82 wk, P = 0.012). Multivariate Cox regression analysis revealed that amplification of D21S1893, D21S1890 and TFF, blood vessel invasion, and staging were associated with poor prognosis.

CONCLUSION: D21S1893-D21S1890 region may harbor candidate genes especially TFF and serine protease family, which might be involved in tumor invasion and metastasis contributing to poor survival. The amplification in this region may be used as a prognostic marker in the treatment of CCA patients.

Keywords: Cholangiocarcinoma; Amplification on chromosome 21; Trefoil factor family; Quantitative PCR; Liver fluke