Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer.
Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer.
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DOI：
10.1038/bjc.2013.108
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发表时间：
2013-04-16
影响因子：
8.8
通讯作者：
Sakamoto N
中科院分区：
文献类型：
--
作者：
Eto K;Kawakami H;Kuwatani M;Kudo T;Abe Y;Kawahata S;Takasawa A;Fukuoka M;Matsuno Y;Asaka M;Sakamoto N
胰腺导管癌（Pancreatic ductal carcinoma，PDC）是人类最致命的恶性肿瘤之一。一些基因的表达模式可以预测吉西他滨（GEM）的治疗效果。我们通过量化PDC患者治疗前内镜超声引导细针穿刺（EUS-FNA）样本中几种基因的表达，研究了GEM治疗患者生存的预测指标。采用实时逆转录-聚合酶链反应对71例不能切除的PDC患者的EUS-FNA组织样本中人平衡型核苷转运蛋白1（hENT 1）、脱氧胞苷激酶、核糖核苷还原酶1、核糖核苷还原酶2和Notch 3的表达进行定量，并检查与GEM敏感性的相关性。对数秩检验发现，在所有检测基因的低和高mRNA水平的GEM治疗患者之间，总生存期无显著差异。然而，在多变量生存分析中，Notch 3 mRNA低表达与较长的总生存期显著相关（P=0.0094）。高hENT 1表达水平与较长的进展时间显著相关（P=0.039）。GEM给药与hENT 1或Notch 3 mRNA表达的相互作用检验具有统计学显著性（分别为P=0.0054和0.0047）。EUS-FNA标本中hENT 1和Notch 3 mRNA表达是不可切除PDC患者GEM疗效和GEM敏感性的关键预测生物标志物。
Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC. The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients with unresectable PDC were quantified using real-time reverse transcription–polymerase chain reactions and examined for correlations with GEM sensitivity. The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and 0.0047, respectively). hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.
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