ERCC1 and BRAC1 mRNA Expression Levels in the Primary Tumor Could Predict the Effectiveness of the Second-Line Cisplatin-Based Chemotherapy in Pretreated Patients with Metastatic Non-small Cell Lung Cancer
ERCC1 and BRAC1 mRNA Expression Levels in the Primary Tumor Could Predict the Effectiveness of the Second-Line Cisplatin-Based Chemotherapy in Pretreated Patients with Metastatic Non-small Cell Lung Cancer
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DOI：
10.1097/jto.0b013e318244bdd4
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发表时间：
2012-04-01
影响因子：
20.4
通讯作者：
Souglakos, John
中科院分区：
文献类型：
--
作者：
Papadaki, Chara;Sfakianaki, Maria;Souglakos, John
简介：研究了 BRCA1 和 ERCC1 表达水平对接受二线铂类化疗的转移性非小细胞肺癌 (NSCLC) 患者的潜在预测作用。方法：采用逆转录后实时定量聚合酶链反应评估 100 例二线接受铂类化疗的初治 NSCLC 患者的显微解剖原发肿瘤中 BRCA1 和 ERCC1 的表达水平。与开始二线治疗后较高的缓解率 (p = 0.011)、较长的中位无进展生存期 (PFS; p = 0.029) 和中位总生存期 (mOS; p - 0.001) 相关。同样，低 BRCA1 表达水平与较高的缓解率 (p = 0.022)、较长的 PFS (p = 0.041) 和 mOS (p = 0.005) 显着相关。此外，与 ERCC1 和 BRCA1 mRNA 均上调的患者相比，ERCC1 和 BRCA1 mRNA 水平较低的患者的中位 PFS (p = 0.021) 和 mOS (p < 0.001) 有所增加。多变量分析显示，低 ERCC1 和低 BRCA1 表达水平与 PFS 增加（分别为风险比 [HR]：0.6；95% 置信区间 [CI]：0.4-0.8；p = 0.029 和 HR：0.7；95% CI：0.6-0.9；p = 0.043）和 OS（HR：0.5；95% CI： 0.3-0.7；p = 0.003；HR：0.7；95% CI：0.6-0.9；p = 0.038。交叉验证研究是必要的。
Introduction: The potential predictive role of BRCA1 and ERCC1 expression levels in patients with metastatic non-small cell lung cancer (NSCLC) receiving second-line platinum-based chemotherapy was investigated.Methods: Real-time quantitative polymerase chain reaction after reverse transcription was used to assess the expression levels of BRCA1 and ERCC1 in 100 microdissected primary tumors from platinum-naive NSCLC patients treated with platinum-based chemotherapy in the second-line setting.Results: Low ERCC1 mRNA levels were significantly associated with higher response rate (p = 0.011), longer median progression-free survival (PFS; p = 0.029), and median overall survival (mOS; p - 0.001) after the initiation of the second-line treatment. Similarly, low BRCA1 expression level was significantly correlated with higher response rate (p = 0.022), longer PFS (p = 0.041), and mOS (p = 0.005). In addition, patients with low ERCC1 and BRCA1 mRNA experienced increased median PFS (p = 0.021) and mOS (p < 0.001) in comparison with those who had both genes upregulated. A multivariate analysis revealed that low ERCC1 and low BRCA1 expression levels were significantly associated with increased PFS (hazard ratio [HR]: 0.6; 95% confidence interval [CI]: 0.4-0.8; p = 0.029 and HR: 0.7; 95% CI: 0.6-0.9; p = 0.043, respectively) and OS (HR: 0.5; 95% CI: 0.3-0.7; p = 0.003 and HR: 0.7; 95% CI: 0.6-0.9; p = 0.038, respectively).Conclusions: These results suggest that the ERCC1 and BRCA1 mRNA expression levels in the primary tumor at the time of diagnosis could be used for the prediction of platinum sensitivity in the treatment of NSCLC in the second-line setting. Cross-validation studies are warranted.