Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy
Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy
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DOI：
10.1007/s00280-014-2562-1
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发表时间：
2014-10-01
影响因子：
3
通讯作者：
Wang, Dong
中科院分区：
文献类型：
--
作者：
Li, Zheng;Qing, Yi;Wang, Dong
耐药性不仅是治疗的主要障碍之一，也是晚期非小细胞肺癌（NSCLC）患者预后不良的原因之一。本研究旨在评估APE1、BRCA1、ERCC1和TUBB3对接受铂类紫杉醇治疗的晚期NSCLC患者的预测价值。本研究纳入了136例接受一线铂类紫杉醇化疗的晚期NSCLC患者。采用免疫组化法评估APE1、BRCA1、ERCC1和TUBB3的蛋白表达水平，并分析其与化疗反应、无进展生存期（PFS）和总生存期（OS）的关系。APE1、ERCC1或TUBB3阴性表达的患者受益于铂加紫杉醇化疗方案。与阳性患者相比，ERCC1 阴性患者的 PFS (P = 0.016) 和 OS (P = 0.030) 更好。同样，APE1 阴性患者表现出更好的 PFS (P = 0.004) 和更长的 OS，尽管统计学上不显着。多变量分析显示，APE1 和 ERCC1 是 PFS（HR 2.07；P = 0.004 和 HR 1.66；P = 0.016）和 OS（HR 1.99；P = 0.008 和 HR 1.64；P = 0.040）的独立预测因子。此外，APE1和ERCC1均为阴性或APE1和TUBB3均为阴性肿瘤的患者在接受铂类和紫杉醇治疗后具有显着更高的缓解率、更长的中位PFS和OS（P < 0.05）。数据表明，APE1、ERCC1和TUBB3可能是预测接受一线铂类紫杉醇化疗的晚期NSCLC患者临床结果的有用生物标志物。
Drug resistance is not only one of the major obstacles to treatment but also a poor prognosis in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the predictive value of APE1, BRCA1, ERCC1 and TUBB3 in advanced NSCLC patients who received platinum-paclitaxel treatment.One hundred and thirty-six advanced NSCLC patients, who were treated with first-line platinum-paclitaxel chemotherapy, were enrolled in this study. The protein expression levels of APE1, BRCA1, ERCC1 and TUBB3 were assessed by immunohistochemistry and analyzed for the association with response to chemotherapy and progression-free survival (PFS) and overall survival (OS).Patients with negative expression of APE1, ERCC1 or TUBB3 benefited from platinum plus paclitaxel regimen chemotherapy. ERCC1-negative patients had better PFS (P = 0.016) and OS (P = 0.030) compared with positive patients. Similarly, the APE1-negative patients showed better PFS (P = 0.004) and longer OS though statistically insignificant. Multivariate analysis showed that APE1 and ERCC1 were independent predictor for PFS (HR 2.07; P = 0.004 and HR 1.66; P = 0.016) and OS (HR 1.99; P = 0.008 and HR 1.64; P = 0.040). Moreover, patients with both APE1- and ERCC1-negative or both APE1- and TUBB3-negative tumors had significantly higher response rate, longer median PFS and OS following treatment with platinum and paclitaxel (P < 0.05).The data indicate that APE1, ERCC1 and TUBB3 could be a useful biomarker to predict clinical outcome in patients with advanced NSCLC receiving first-line platinum-paclitaxel chemotherapy.