Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma
Human Equilibrative Nucleoside Transporter 1 and Human Concentrative Nucleoside Transporter 3 Predict Survival after Adjuvant Gemcitabine Therapy in Resected Pancreatic Adenocarcinoma
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DOI：
10.1158/1078-0432.ccr-08-2080
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发表时间：
2009-04-15
影响因子：
11.5
通讯作者：
Van Laethem, Jean-Luc
中科院分区：
文献类型：
--
作者：
Marechal, Raphael;Mackey, John R.;Van Laethem, Jean-Luc
目的：吉西他滨是胰腺癌切除术后的一种有前景的辅助治疗方法，其与放疗联合使用正在探索中。人平衡型核苷转运蛋白1（hENT 1）和人浓缩型核苷转运蛋白（hCNT）1和3是负责将2 '，2'-二氟-2-脱氧胞苷（吉西他滨）摄取到细胞中的主要转运蛋白。本研究的目的是根据术后基于吉西他滨的放化疗方案后肿瘤细胞中hENT 1和hCNT 3的表达来确定患者的结局。实验设计：我们研究了45例胰腺癌患者在根治性切除术后接受基于吉西他滨的放化疗治疗的肿瘤块，并使用免疫组织化学评估hENT 1和hCNT 3的表达。当调整淋巴结比率和肿瘤直径的影响时，hENT 1高表达的患者比低表达的患者具有显著更长的无病生存期和总生存期（OS），而hCNT 3高表达仅与更长的OS相关。具有两个有利预后因素的患者（hENT 1（高）/hCNT 3（高）表达）具有较长的存活期，（中位OS，94.8个月）（中位OS，18.7个月）或无（中位OS，12.2个月）有利的预后因素。hENT 1和hCNT 3免疫染色高表达的胰腺癌患者在吉西他滨辅助放化疗后生存期显著延长。这些生物标志物值得在接受基于吉西他滨的辅助治疗的患者中进行前瞻性评价。
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 (hENT1(high)/hCNT3(high) 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.