ERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer
ERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer
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DOI：
10.1097/jto.0b013e318155a637
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发表时间：
2007-10-01
影响因子：
20.4
通讯作者：
Thatcher, Nick
中科院分区：
文献类型：
--
作者：
Booton, Richard;Ward, Tim;Thatcher, Nick
背景：以铂类为基础的治疗是晚期非小细胞肺癌（NSCLC）治疗的关键。切除修复交叉互补组I（ERCC 1）是负责核苷酸切除修复的铂-DNA修复机制的关键组分。我们试图确定ERCC 1 mRNA表达在晚期NSCLC化疗反应，毒性和生存后，铂为基础的chemotherapy.Methods的影响：患者随机分为III期试验的铂为基础的化疗有资格列入。福尔马林固定的石蜡包埋的肿瘤活检组织进行检索的mRNA提取和纯化，然后使用Taqman技术进行定量实时聚合酶链反应分析。表达数据与治疗反应、毒性和总生存率相关。ERCC 1 mRNA表达与化疗反应（p = 0.794）或血液学毒性之间无统计学显著相关性。根据ERCC 1表达，中位生存期无统计学显著差异（高表达，415天，95%置信区间[95%CI]：197-633天;低表达。327天[95%CI：211-433天]; p = 0.801）。ERCC 1 mRNA高表达与死亡风险比为0.96（95%CI 0.919-1.004; p = 0.08）相关。结论：与近期发表的文献相比，本研究中ERCC 1 mRNA表达并不有利于晚期NSCLC患者铂类药物化疗后的预后。我们探讨了潜在的原因，包括需要谨慎的解释mRNA表达数据的档案材料和highli 2 ht需要额外的翻译研究连接基因表达与一个有前途的ERCC 1多态性。
Background: Platinum-based therapy is pivotal to the treatment of advanced non-small cell lung Cancer (NSCLC). Excision repair cross-complementation group I (ERCC 1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. We sought to determine the influence of ERCC1 mRNA expression in advanced NSCLC on chemotherapy response, toxicity, and survival after platinum-based chemotherapy.Methods: Patients randomized to a phase III trial of platinum-based chemotherapy were eligible for inclusion. Formalin-fixed paraffin-embedded tumor biopsies were retrieved for mRNA extraction and purification before quantitative real-time polymerase chain reaction analysis using Taqman technology. Expression data were correlated with treatment response, toxicity, and overall survival.Results: Sixty-six patients were enrolled. No statistically significant relationship existed between ERCC1 mRNA expression and response to chemotherapy (p = 0.794) or hematological toxicity. No statistically significant difference in median survival was demonstrated according to ERCC1 expression (high expression, 415 days, 95% confidence interval [95%CI]: 197-633 days; low expression. 327 days [95%CI: 211-433 days]; p = 0.801). High ERCC1 mRNA expression was associated with a hazard ratio for death of 0.96 (95% Cl 0.919-1.004; p = 0.08).Conclusion: In contrast to recent publications, ERCC1 mRNA expression in our study did not favor a prognostically better outcome after platinum-based chemotherapy in advanced NSCLC. We explore potential reasons for this, including the need for cautious interpretation of mRNA expression data from archival materials and highli2ht the need for additional translational research linking gene expression with a promising ERCC1 polymorphism.