Simple combinations of 5-FU pathway genes predict the outcome of metastatic gastric cancer patients treated by S-1
Simple combinations of 5-FU pathway genes predict the outcome of metastatic gastric cancer patients treated by S-1
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DOI：
10.1002/ijc.22080
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发表时间：
2006-10-15
影响因子：
6.4
通讯作者：
Hirayama, Renzo
中科院分区：
文献类型：
--
作者：
Ichikawa, Wataru;Takahashi, Takehiro;Hirayama, Renzo
我们评估了从原发性肿瘤中获得的化疗前新鲜冷冻样本中5-FU途径基因的表达，以预测59例接受S-1单药治疗作为一线治疗的转移性胃癌患者的缓解和生存。采用实时荧光定量RT-PCR方法检测5-FU途径基因，包括胸苷酸合成酶（TS）、二氢嘧啶脱氢酶（DPD）、乳清酸磷酸核糖转移酶（OPRT）、胸苷磷酸化酶（TP）和尿苷磷酸化酶（UP）。选择每个基因的中值作为分离高和低基因表达的截止值。在单变量分析中，低TS、高OPRT和低TP与肿瘤缩小和长生存期显著相关，而DPD和UP基因表达与反应和生存期无关。多变量分析显示，独立变量为OPRT和TS的反应和TS和TP的生存。当OPRT和TS相结合时，观察到反应的准确率显著增加至91.5%。同样，与高TS或高TP患者相比，低TS和低TP患者的生存风险比增加10.29。2个基因的简单组合，OPRT和TS的反应和TS和TP的生存，可能允许识别胃癌患者谁将受益于S-1化疗。(c)2006 Wiley-Liss，Inc.
We evaluated the expression of 5-FU pathway genes in prechemotherapeutic fresh frozen samples obtained from primary tumors to predict response and survival of 59 metastatic gastric cancer patients treated with S-1 monotherapy as first line treatment. Five 5-FU pathway genes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP) and uridine phosphorylase (UP), were analyzed by the quantitative real-time reverse transcriptional PCR method. Median values of each gene were selected for cut-off values separating high and low gene expressions. In univariate analyses, low TS, high OPRT and low TP were significantly associated with a tumor shrinkage and a long survival, whereas DPD and UP gene expressions did not correlate with response and survival. Multivariate analyses revealed that independent variables were OPRT and TS for response and TS and TP for survival. When OPRT and TS were combined, a significantly increased accuracy rate of 91.5% was seen for response. Similarly, an increased hazard ratio of 10.29 was observed for survival in patients possessing low TS and low TP, compared with those with high TS or high TP. The simple combinations of 2 genes, OPRT and TS for response and TS and TP for survival, may allow identification of gastric cancer patients who will benefit from S-1 chemotherapy. (c) 2006 Wiley-Liss, Inc.