晚期非小细胞肺癌胸腔积液表皮生长因子受体突变检测对厄洛替尼疗效的预测价值
Value of the detection of epidermal growth factor receptor mutation in pleural effusion of patients with advanced non-small cell lung cell in predicting the curative effect of erlotinib
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摘要: 目的：探讨非小细胞肺癌（NSCLC）患者胸腔积液（胸液）表皮生长因子受体（EGFR）突变对厄洛替尼疗效的预测价值。方法：应用实时荧光定量PCR-HRM法检测275例NSCLC患者胸液标本EGFR突变，其中有组织标本的52例同时进行HRM法和直接测序法检测，比较胸液与组织EGFR突变状态的一致性和可重复性。胸液EGFR敏感突变患者随机给予厄洛替尼治疗或吉西他滨加顺铂（GP）方案化疗。比较2组客观缓解率（ORR）和中位无进展生存期（mPFS）。结果：275例NSCLC患者胸液EGFR敏感突变率为55.3%。52例配对组织、胸液标本中，EGFR敏感突变检出率为61.5%，高于直接测序法的40.3%（P<0.01）；胸液标本中，EGFR敏感突变检出率为55.8%，高于直接测序法的36.5%（P<0.01）。胸液和组织检测EGFR敏感突变的吻合率为82.6%；厄洛替尼组mPFS 11.5个月（95%CI 10.4~12.6），显著高于GP组的4.4个月（95%CI 3.9~4.8）（P<0.01）。厄洛替尼组ORR明显高于GP组（70.0% vs 29.4%，P<0.01）。结论：晚期NSCLC胸液标本可弥补或替代组织标本进行EGFR敏感突变检测，HRM法敏感性优于直接测序法。EGFR敏感突变NSCLC患者应用厄洛替尼可提高客观缓解率，延长mPFS。Abstract: Objective: To investigate the value of the detection of epidermal growth factor receptor(EGFR) gene mutation in pleural effusion of patients with advanced non-small cell lung cell(NSCLC) in predicting the curative effect of Erlotinib.Methods: The EGFR gene mutation in pleural effusion of 275 patients with NSCLC were detected using PCR-HRM,and 52 tissue samples were detected using HRM and direct sequencing.The consistency and repeatability of EGFR mutation in pleural effusion and tissue specimens were compared,respectively.The EGFR mutation sensitive patients were randomly treated with the erlotinib or gemcitabine cisplatin therapy.The objective response rate(ORR) and median progression-free survival(mPFS) between two groups were compared.Results: The sensitive mutation rate of EGFR in pleural effusion of 275 NSCLC patients was 55.3%.Among the pairing tissue specimens and pleural effusion of 52 cases,the sensitive mutation rate of EGFR was 61.5%,which was higher than that using the direct sequencing(40.3%)(P<0.01).The sensitive mutation rate of EGFR in pleural effusion was 55.8%,which was higher than that using direct sequencing(36.5%)(P<0.01).The coincidence rate of the EGFR mutation in tissue specimen and pleural effusion was 82.6%.The mPFS in Erlotinib group was 11.5 months(95%CI for 10.4 to 12.6),which was higher than 4.4 months in GP group(95%CI for 3.9 to 4.8)(P<0.01).The ORR in Erlotinib group(70.0%) was significantly higher than that in GP group(29.4%)(P<0.01).Conclusions: Among the patients with advance NSCLC,the sensitive mutation detection of EGFR in pleural effusion can compensate or replace the detection of tissue specimens,and the sensibility of HRM is better than that of direct sequencing.The application of Erlotinib in NSCLC patients with EGFR sensitive mutation can improve the ORR,and prolong mPFS.
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