Super-ARMS法检测肺腺癌患者血浆循环肿瘤DNA表皮生长因子受体T790M基因突变的临床研究  

Clinical application of the Super-ARMS assay for detecting epidermal growth factor receptor T790M mutations in plasma circulating tumor DNA in patients with lung adenocarcinoma

作　　者：周傲雪 史亮 李琨 车南颖[1] 刘喆[1] Aoxue Zhou;Liang Shi;Kun Li;Nanying Che;Zhe Liu(Beijing Tuberculosis and Thoracic Tumor Research Institute/Department of Oncology,Beijing Chest Hospital,Capital Medical University,Beijing 101149,China)

机构地区：[1]北京市结核病胸部肿瘤研究所/首都医科大学附属北京胸科医院肿瘤一科,北京市101149

出　　处：《中国肿瘤临床》2021年第15期767-771,共5页Chinese Journal of Clinical Oncology

摘　　要：目的:探讨真实世界中Super-ARMS法检测肺腺癌患者外周血标本循环肿瘤脱氧核糖核酸(circulating tumor DNA,ctDNA)中表皮生长因子受体(epidermal growth factor receptor,EGFR)T790M基因突变的临床应用价值。方法:收集2019年1月至2020年6月在首都医科大学附属北京胸科医院确诊的肺腺癌患者307例,突变扩增系统(amplification refractory mutation system,ARMS)检测组织中EGFR基因突变情况,Super-ARMS法检测血浆中EGFR的基因突变情况。通过生存分析比较不同标本检测EGFR T790M基因突变患者的无进展生存时间(progression-free survival,PFS)。结果:153例患者疾病进展接受再活检。74例进行组织再活检,其中34例(45.9%)检测到EGFR T790M基因突变。141例患者进行液体再活检,其中51例(36.2%)EGFR T790M基因突变。Kaplan-Meier生存分析显示,组织和外周血EGFR T790M突变阳性患者接受第三代EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)的中位PFS比较差异无统计学差异(16.3个月vs.11.4个月,x2=1.138,P>0.05)。组织和外周血EGFR T790M突变阴性患者未接受第三代EGFR-TKIs治疗的中位PFS比较差异无统计学意义(7.0个月vs.7.0个月,x2=0.470,P>0.05)。结论:真实世界中Super-ARMS法检测外周血标本有望应用于检测EGFR T790M基因突变情况,外周血标本可一定程度上补充组织标本检测EGFR T790M基因突变结果,预测患者对第三代EGFR-TKIs治疗的疗效。Objective:To investigate the clinical value of the Super-ARMS assay in detecting epidermal growth factor receptor(EGFR)T790M mutations in circulating tumor DNA(ctDNA)in plasma samples of lung cancer patients in real-world settings.Methods:A total of 307 patients with lung cancer diagnosed in Beijing Chest Hospital from January 2019 to June 2020 were enrolled.EGFR mutations in tumor tissues were detected by the amplification refractory mutation system(ARMS),and EGFR mutations in plasma were detected by the Super-ARMS assay.The progression-free survival(PFS)of patients with EGFR T790M mutations was compared according to the samples using different methods of detection;survival analysis was performed for this purpose.Results:Of the 307 patients,153 underwent re-biopsy for disease progression.EGFR T790M mutations were detected in 34 of 74(45.9%)patients after tissue re-biopsy.EGFR T790M gene mutations in plasma ctDNA were detected in 51 of 141(36.2%)patients.Kaplan–Meier survival analysis showed that there was no significant difference in the median PFS of tissue EGFR T790M mutation-positive and plasma EGFR T790M mutation-positive patients who received third-generation of EGFR-tyrosine kinase inhibitors(EGFR-TKIs)(16.3 vs.11.4 months,x2=1.138,P>0.05).There was no significant difference in the median PFS of tissue EGFR T790M mutation-negative and plasma EGFR T790M mutation-negative patients who did not receive third-generation EGFR-TKIs(7.0 vs.7.0 months,x2=0.47,P>0.05).Conclusions:The application of Super-ARMS-based detection of EGFR T790M mutations using peripheral blood samples is promising;plasma samples can replace tissue samples to a certain extent for the detection of EGFR T790M mutations and for predicting the efficacy of third-generation EGFR-TKIs.

关 键 词：肺腺癌 表皮生长因子受体 基因突变 循环肿瘤脱氧核糖核酸 突变扩增系统 

分 类 号：R734.2[医药卫生—肿瘤]