人类平衡核苷转运蛋白 1 表达是接受术前吉西他滨为基础的放化疗的 UICC T3-T4 胰腺癌患者的一个强有力的独立预后因素。

Human equilibrative nucleoside transporter 1 expression is a strong independent prognostic factor in UICC T3-T4 pancreatic cancer patients treated with preoperative gemcitabine-based chemoradiotherapy.

机构信息

Department of Hepatobiliary Pancreatic and Transplant Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan.

出版信息

J Hepatobiliary Pancreat Sci. 2012 Jul;19(4):413-25. doi: 10.1007/s00534-011-0440-3.

DOI:10.1007/s00534-011-0440-3

PMID:21898089

Abstract

BACKGROUND/PURPOSE: We aimed to determine the relationship between the intratumoral expression of human equilibrative nucleoside transporter (hENT1), the main gemcitabine transporter into cells, and the outcome of gemcitabine-based chemoradiotherapy (Gem-CRT) in patients with International Union Against Cancer (UICC) T3-T4 pancreatic adenocarcinoma.

METHODS

The expressions of hENT1, thymidylate synthase (TS), and dihydropyrimidine dehydrogenase were immunohistochemically analyzed using the resected specimens from 55 patients (T3, 38 and T4, 17) who had received curative-intent resection after Gem-CRT.

RESULTS

The status of hENT1 expression (positive in 39 and negative in 16) was significantly associated with "clinical efficacy" (defined as more than 50% reduction of the serum carbohydrate antigen [CA] 19-9 level with stable disease [SD] or partial response [PR] according to the Response Evaluation Criteria in Solid Tumors [RECIST]) for Gem-CRT. The 1- and 3-year overall survival (OS) rates were significantly higher in the positive hENT1 expression group (82.9, 39.5%) than in the negative expression group (42.9, 14.3%) (p = 0.0037). According to combination analysis of hENT1 and TS expressions, the 1- and 3-year OS rates were significantly higher in the positive-low combination (89.1, 51.0%) group than in the negative-high group (66.7, 0%) (p = 0.023). Multivariate analysis revealed that positive hENT1 expression and R0 resection were significant prognostic factors for OS.

CONCLUSIONS

The hENT1 expression in pancreatic adenocarcinoma strongly influences the outcome of preoperative Gem-CRT treatment. This biomarker could become a useful predictor of therapeutic effect for gemcitabine-based therapy in pancreatic cancer patients.

摘要

背景/目的：我们旨在确定细胞内主要吉西他滨转运体——人嘧啶核苷转运蛋白 1（hENT1）的肿瘤内表达与国际抗癌联盟（UICC）T3-T4 期胰腺腺癌患者接受吉西他滨为基础的放化疗（Gem-CRT）后结局之间的关系。

方法

使用 55 例接受 Gem-CRT 后根治性切除的患者（T3 期 38 例，T4 期 17 例）的切除标本，通过免疫组织化学分析 hENT1、胸苷酸合成酶（TS）和二氢嘧啶脱氢酶的表达。

结果

hENT1 表达状态（阳性 39 例，阴性 16 例）与 Gem-CRT 的“临床疗效”显著相关（根据实体瘤反应评估标准 [RECIST]，定义为血清碳水化合物抗原 [CA] 19-9 水平降低 50%以上，稳定疾病[SD]或部分缓解[PR]）。hENT1 阳性表达组的 1 年和 3 年总生存率（OS）显著高于 hENT1 阴性表达组（82.9%，39.5%；p=0.0037）。根据 hENT1 和 TS 表达的联合分析，阳性低表达组（89.1%，51.0%）的 1 年和 3 年 OS 率显著高于阴性高表达组（66.7%，0%；p=0.023）。多变量分析显示，hENT1 阳性表达和 R0 切除是 OS 的显著预后因素。