Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy
Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy
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DOI：
10.1093/annonc/mdl435
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发表时间：
2007-03-01
影响因子：
50.5
通讯作者：
Baselga, J.
中科院分区：
文献类型：
--
作者：
Bellmunt, J.;Paz-Ares, L.;Baselga, J.
背景：基于化疗敏感性预测进行化疗方案定制可能会改善晚期膀胱癌患者的预后。由于DNA损伤剂是治疗的基石，我们假设DNA修复基因的水平能够预测生存期。
患者与方法：通过逆转录聚合酶链反应（RT - PCR）测定57例接受吉西他滨/顺铂或吉西他滨/顺铂/紫杉醇（泰素）治疗的晚期和转移性膀胱癌患者肿瘤DNA中切除修复交叉互补基因1（ERCC1）、乳腺癌1号基因（BRCA1）、核糖核苷酸还原酶亚基M1（RRM1）和窖蛋白-1的信使RNA表达水平。这些水平与生存期、疾病进展时间和化疗反应相关。
结果：ERCC1水平低的患者中位生存期明显更高（25.4个月对15.4个月；P = 0.03）（中位随访19个月）。在所有标志物表达水平均较低的肿瘤患者中，观察到疾病进展时间有延长的趋势。然而，RRM1、BRCA1和窖蛋白-1的水平无法预测生存期，且与化疗反应之间也无法建立明确的联系。在对预处理预后因素进行多变量分析时，ERCC1成为生存期的一个独立预测因素。
结论：该研究结果表明，ERCC1可能预测以铂类为基础治疗的膀胱癌患者的生存期。
Background: Customizing chemotherapy on the basis of chemosentitivity prediction may improve outcome in advanced bladder cancer patients. Since DNA damaging agents are the cornerstones of therapy, we hypothesized that levels of DNA repair genes could predict survival.Patients and methods: Messenger RNA expression levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT-PCR in tumor DNA from 57 advanced and metastatic bladder cancer patients treated with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol). Levels were correlated with survival, time to disease progression and chemotherapy response.Results: Median survival was significantly higher in patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow-up 19 months). A trend towards longer time to progression was observed in patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1 and caveolin-1, however, failed to predict the survival and a clear link with chemotherapy response could not be established. On multivariate analysis with pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for survival.Conclusion: The results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy.