Polymerase η mRNA Expression Predicts Survival of Non - Small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy
Polymerase η mRNA Expression Predicts Survival of Non - Small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy
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DOI：
10.1158/1078-0432.ccr-08-1227
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发表时间：
2009-02-01
影响因子：
11.5
通讯作者：
Scagliotti, Giorgio
中科院分区：
文献类型：
--
作者：
Ceppi, Paolo;Novello, Silvia;Scagliotti, Giorgio
目的：最近研究了翻译DNA合成系统在赋予细胞对DNA损伤剂的耐受性方面的作用。DNA聚合酶（Pol eta）是该机制的一部分，体外模型表明它可以克服顺铂和紫外线引起的DNA损伤。本研究的目的是探讨Pol - 11mrna表达水平在非小细胞肺癌（NSCLC）中的作用。实验设计：通过实时荧光定量PCR （real-time PCR）评估(a) 72例接受铂类化疗的NSCLC患者的福尔马林固定石蜡包埋活检组织，(b) 50例连续未接受围手术期或术后化疗的患者的新鲜快速冷冻手术肿瘤标本和相应的正常肺组织，以及(c) 5个NSCLC细胞系的Pol eta mRNA表达水平。结果：高Pol I I表达水平与铂治疗组患者的单因素（6.9 vs 21.1个月，P = 0.003）和多因素（风险比，3.18；95%可信区间，1.73-5.84,P = 0.008）分析中较短的生存期密切相关。相比之下，手术切除患者的Pol eta表达与预后无显著相关性（P = 0.54），肿瘤与正常肺的mRNA水平无显著差异（P = 0.82）。此外，5种细胞系中有3种可被顺铂诱导内源性Pol eta mRNA表达，并与体外敏感性显著相关（P = 0.01）。结论：综上所述，这些数据表明，Pol eta作为一种预测指标而非预后指标，值得对候选铂类化疗的NSCLC患者进行进一步研究。
Purpose: The effect of translesion DNA synthesis system in conferring cellular tolerance to DNA-damaging agents has been recently described. DNA polymerase eta (Pol eta) is part of this machinery and in vitro models showed that it can overcome DNA damages caused by cisplatin and UV rays. The aim of the present study was to investigate the role of Pol 11 mRNA expression levels in non - small cell lung cancer (NSCLC).Experimental Design: Pol eta mRNA expression levels were evaluated by real-time PCR in (a) formalin-fixed paraffin-embedded biopsies of 72 NSCLC patients treated with platinum-based chemotherapy, (b) fresh snap-frozen surgical specimens of tumor and corresponding normal lung tissue from 50 consecutive patients not treated with perioperative or postoperative chemotherapy, and (c) five NSCLC cell lines.Results: High Pol I I expression levels were strongly associated with shorter survival at both univariate (6.9 versus 21.1 months; P = 0.003) and multivariate (hazard ratio, 3.18; 95% confidence interval, 1.73-5.84; P = 0.008) analysis in the group of platinum-treated patients. By contrast, Pol eta expression was not significantly correlated with the prognosis in surgically resected patients (P = 0.54) and mRNA levels did not significantly differ in tumor versus normal lung (P = 0.82). Moreover, endogenous Pol eta mRNA expression was found to be inducible by cisplatin in three of five cell lines and significantly associated with in vitro sensitivity (P = 0.01).Conclusions: Taken together, these data indicate Pol eta as a predictive rather than prognostic marker worth of further investigation in NSCLC patients candidate to platinum-based chemotherapy.