Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma
Open Access
- 15 April 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 15 (8), 2913-2919
- https://doi.org/10.1158/1078-0432.ccr-08-2080
Abstract
Purpose: Gemcitabine is a promising adjuvant treatment for patients with resected pancreatic adenocarcinoma and its use in combination with radiotherapy is under exploration. Human equilibrative nucleoside transporter 1 (hENT1) and human concentrative nucleoside transporter (hCNT) 1 and 3 are the major transporters responsible for 2′,2′-difluoro-2-deoxycytidine (gemcitabine) uptake into cells. The aim of this study was to determine patients' outcome according to the expression of hENT1 and hCNT3 in tumoral cells after postoperative gemcitabine-based chemoradiation regimen. Experimental Design: We studied tumor blocks from 45 pancreatic adenocarcinoma patients treated with gemcitabine-based chemoradiation after curative resection and assessed hENT1 and hCNT3 expression using immunohistochemistry. Results: When adjusted for the effects of lymph node ratio and tumor diameter, patients with high hENT1 expression had significantly longer disease-free survival and overall survival (OS) than patients with low expression, whereas high hCNT3 expression was only associated with longer OS. In a combined analysis, patients with two favorable prognostic factors (hENT1high/hCNT3high expression) had a longer survival (median OS, 94.8 months) than those having one (median OS, 18.7 months) or no (median OS, 12.2 months) favorable prognostic factor. Conclusions: Pancreatic adenocarcinoma patients with a high expression of hENT1 and hCNT3 immunostaining have a significantly longer survival after adjuvant gemcitabine-based chemoradiation. These biomarkers deserve prospective evaluation in patients receiving gemcitabine-based adjuvant therapy.Keywords
This publication has 33 references indexed in Scilit:
- Modulation of the human equilibrative nucleoside transporter1 (hENT1) activity by IL-4 and PMA in B cells from chronic lymphocytic leukemiaBiochemical Pharmacology, 2008
- Long-term Survival and Metastatic Pattern of Pancreatic and Periampullary Cancer After Adjuvant Chemoradiation or ObservationAnnals of Surgery, 2007
- HUMAN ENT1 IS PREDICTIVE OF RESPONSE IN PATIENTS WITH PANCREATIC CANCER TREATED WITH GEMCITABINEPancreas, 2007
- Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cellsBritish Journal of Cancer, 2007
- Characterization and Functional Analysis of the Promoter for the Human Equilibrative Nucleoside Transporter Gene, hENT1Nucleosides, Nucleotides and Nucleic Acids, 2007
- The Absence of Human Equilibrative Nucleoside Transporter 1 Is Associated with Reduced Survival in Patients With Gemcitabine-Treated Pancreas AdenocarcinomaClinical Cancer Research, 2004
- A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic CancerNew England Journal of Medicine, 2004
- Differential Expression of Human Nucleoside Transporters in Normal and Tumor TissueBiochemical and Biophysical Research Communications, 2001
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958
- Nonparametric Estimation from Incomplete ObservationsJournal of the American Statistical Association, 1958