Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial
Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial
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DOI：
10.1093/jnci/djt347
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发表时间：
2014-01-01
影响因子：
10.3
通讯作者：
Buechler, Markus W.
中科院分区：
文献类型：
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作者：
Greenhalf, William;Ghaneh, Paula;Buechler, Markus W.
背景人类平衡核苷转运蛋白1（hENT 1）在胰腺癌的水平可以预测谁接受辅助吉西他滨切除术后survival.Methods从434例患者随机化疗ESPAC-3试验（加上对照组ESPAC-1/3）的微阵列与10 D 7 G2抗hENT 1抗体染色。如果患者核心的平均H评分高于总体中位H评分，则将患者归类为hENT 1高表达（48）。使用Kaplan-Meier曲线、对数秩检验和考克斯比例风险模型比较hENT 1高表达组和低表达组。结果380例（87.6%）患者和1808个核心数据符合要求，并纳入最终分析。吉西他滨治疗患者（n = 176）的中位总生存期为23.4（95%置信区间[CI] = 18.3 - 26.0）个月vs 23.5个月176例接受5-氟尿嘧啶/亚叶酸治疗的患者的（95% CI = 19.8 - 27.3）个月（176名接受5-氟尿嘧啶/亚叶酸治疗的患者的月数与23.5（95%CI = 19.8至27.3）个月（chi（2）（1）=0.24; P = 0.62）。hENT 1低表达患者接受吉西他滨治疗的中位生存期为17.1（95%CI = 14.3 - 23.8）个月，而hENT 1高表达患者接受吉西他滨治疗的中位生存期为26.2（95%CI = 21.2 - 31.4）个月（chi（2）（1）=9.87; P = .002）。对于5-氟尿嘧啶组，hENT 1低表达和高表达患者的中位生存期分别为25.6（95% CI = 20.1至27.9）和21.9（95% CI = 16.0至28.3）个月（chi（2）（1）= 0.83; P = 0.36）。hENT 1水平不能预测观察组28例患者的生存率（卡方检验（2）（1）= 0.37; P = 0.54）。多变量分析证实hENT 1表达是吉西他滨治疗（Wald chi（2）（1）= 9.16; P = 0.003）而不是5-氟尿嘧啶治疗（Wald chi（2）（1）= 1.22; P = 0.27）患者的预测标志物。
Background Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.Methods Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided.Results Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (chi(2)(1)=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (chi(2)(1)=9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (chi(2)(1) = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (chi(2)(1) = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald chi(2)(1) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald chi(2)(1) = 1.22; P = .27) patients.Conclusions Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.