Overexpression of the Mammalian Target of Rapamycin A Novel Biomarker for Poor Survival in Resected Early Stage Non-small Cell Lung Cancer
Overexpression of the Mammalian Target of Rapamycin A Novel Biomarker for Poor Survival in Resected Early Stage Non-small Cell Lung Cancer
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DOI：
10.1097/jto.0b013e3181ce6604
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发表时间：
2010-03-01
影响因子：
20.4
通讯作者：
Seckl, Michael J.
中科院分区：
文献类型：
--
作者：
Dhillon, Tony;Mauri, Francesco A.;Seckl, Michael J.
前言：非小细胞肺癌（NSCLC）患者治愈的最佳希望是手术切除。然而，即使在IA期患者中，也有30%在5年内死亡。生存率的进一步改善需要一种生物标志物，它定义了这些注定会表现不好的患者的子集，以便他们可以成为额外治疗的目标。在这里，我们调查是否免疫组化表达的关键激酶牵连在肺癌生物学，哺乳动物的雷帕霉素靶（mTOR）可以预测生存结果与早期切除NSCLC患者。材料和方法：134例切除早期（IA-IIB）NSCLC患者进行了病理检查，染色mTOR前集中。通过单变量和多变量分析评估了多个变量，包括年龄、性别、分期、血管浸润、淋巴结状态和mTOR染色。结果：分期（p = 0.044）、淋巴结状态（p = 0.049）、血管浸润（p = 0.017）和mTOR染色（p = 0.007）是不良生存率的显著单变量预测因子。然而，在多变量分析后，仅血管浸润（p = 0.016）和mTOR染色（p = 0.046）仍具有显著性。此外，mTOR染色是预测淋巴结阴性（p = 0.016）或IA期（p = 0.0016）患者预后不良的唯一变量。结论：mTOR染色为早期NSCLC的预后不良提供了一种新的生物标志物，并且可以使切除的IA期患者能够被选择用于可能使用mTOR抑制剂的新疗法。
Introduction: The best hope of cure for patients with non-small cell lung cancer (NSCLC) is surgical resection. However, even in stage IA patients, 30% die within 5 years. Further improvements in survival require a biomarker(s), which defines the subset of these patients destined to do badly so that they could be targeted for additional therapies. Here, we investigate whether the immunohistochemical expression of a key kinase implicated in lung cancer biology, the mammalian target of rapamycin (mTOR) can predict survival outcome in patients with early stage resected NSCLC.Materials and Methods: One hundred thirty-four patients with resected early stage (IA-IIB) NSCLC were pathologically reviewed centrally before staining for mTOR. Multiple variables including age, sex, stage, angioinvasion, lymph node status, and mTOR staining were assessed by univariate and multivariate analyses.Results: Stage (p = 0.044), lymph node status (p = 0.049), angioinvasion (p = 0.017), and mTOR staining (p = 0.007) were significant univariate predictors of poor survival. However, only angioinvasion (p = 0.016) and mTOR staining (p = 0.046) remained significant after multivariate analysis. Moreover, mTOR staining was the only variable to predict poor outcome in patients who either had negative lymph nodes (p = 0.016) or were stage IA (p = 0.0016).Conclusions: The mTOR staining provides a new biomarker for poor outcome in early stage NSCLC and could enable resected stage IA patients to be selected for novel therapies possibly with an mTOR inhibitor.