Li Zheng, Qing Yi, Guan Wei, Li Mengxia, Peng Yu, Zhang Shiheng, Xiong Yanli, Wang Dong
Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, No. 10 Changjiang Zhi Rd., Yuzhong District, Chongqing, 400042, China.
Cancer Chemother Pharmacol. 2014 Oct;74(4):777-86. doi: 10.1007/s00280-014-2562-1. Epub 2014 Aug 9.
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.
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）患者预后不良的因素。本研究的目的是评估APE1、BRCA1、ERCC1和TUBB3在接受铂类-紫杉醇治疗的晚期NSCLC患者中的预测价值。
136例接受一线铂类-紫杉醇化疗的晚期NSCLC患者纳入本研究。通过免疫组织化学评估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）的相关性。
APE1、ERCC1或TUBB3表达阴性的患者从铂类加紫杉醇方案化疗中获益。与ERCC1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阴性患者的PFS（P = 0.004）更好，OS更长，尽管在统计学上无显著差异。多因素分析显示，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）的独立预测因素。此外，APE1和ERCC1均为阴性或APE1和TUBB3均为阴性的肿瘤患者，在接受铂类和紫杉醇治疗后的缓解率显著更高，中位PFS和OS更长（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患者临床结局的有用生物标志物。
