检测肺癌患者血清游离DNA的EGFR基因点突变与EGFR-TKI疗效的相关性分析  

Correlation analysis of serum free DNA EGFR mutation and EGFR-TKI response in lung cancer patients

作　　者：周小昀[1] 李龙芸[1] 崔巍[2] 王树兰[1] 王孟昭[1] 翁姗姗[1] 钟巍[1] 张力[1] 张晓彤[1] 徐丽艳[3] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院呼吸内科,北京100730 [2]中国医学科学院北京协和医学院北京协和医院检验科,北京100730 [3]北京胸科医院,北京101149

出　　处：《癌症进展》2011年第1期13-18,共6页Oncology Progress

摘　　要：目的探讨测定肺癌患者血清游离DNA的EGFR基因点突变的可行性,及检测结果与肺癌患者对EGFR-TKI疗效间的相关性。方法收集2007年11月～2008年4月170份北京协和医院呼吸内科肺癌中心门诊就诊患者4ml全血的血清样本,经检查后确诊为非恶性肺疾病20例,肺癌150例,其中腺癌140例,鳞癌10例。蝎形探针扩增阻滞突变系统(Scorpions ARMS)检测外周血清游离DNA中EGFR基因点突变情况。结果 150份肺癌患者血清标本检测到87个突变,敏感突变49例(32.7%),耐药突变38例(25.3%),敏感/耐药双突变7例(8.0%);敏感突变率女性中显著高于男性,分别为40.2%及22.2%(P<0.05)。非吸烟者高于吸烟者,分别为55.7%和22.5%(P<0.01);140例肺腺癌敏感突变率为35.0%,应用EGFR-TKI的有效率达83.0%;T790M为常见耐药突变,与应用EGFR-TKI可能有关,且显示疾病可能进展或耐药。结论 Scorpions ARMS检测肺癌患者外周血清游离DNA的EGFR基因点突变方法取材方便、方法灵敏及重复性好;EGFR基因点突变检测结果与临床评估EGFR-TKI疗效较为符合,因此在预测疗效、监测耐药发生方面,有良好的临床应用前景。Objective To explore the feasibility of Scorpions ARMS testing EGFR mutation using serum free DNA samples and the correlation between the EGFR mutation status and TKI response in lung cancer patients. Methods To- tally 170 serum samples were collected from Peking Union Medical College Hospital Respiratory Clinic, which included 20 cases of benign diseases and 150 cases of lung cancer （adenoearcinoma/squamous 140/10）. QLAGEN Blood Mini Kit was used for sermn free DNA extraction and DxS RT-PCR Kit for detecting EGFR mutation from the condensed DNA. Resuits Eighty-seven EGFR gene mutations were detected in the serum samples of 150 lung cancer patients, with 49（32.7%） sensitive mutations and 38 （25.3%） resistant nmtations and 7 （8.0%） cases of doublet. Female nonsmokers had significantly higher mutation rate than males and smokers. Of 140 patients with adenocarcinoma, 35.0% had sensitive mutations, and the responsiveness with EGFR-TKIs was 83.0%. The efficacy of EGFR-TKIs was often limited because of the drug resistance cont^rred by T790M. Conclusion EGFR mutation detected with Scorpions ARMS Kit using serum free DNA of lung caneer is convenient and highly sensitive. The results are consistent with the clinical evaluation resutls of EGFR-TKI. h is therefore promising in predicting treatment effectiveness and multiple drug resistance.

关 键 词：非小细胞肺癌 血清游离DNA 表皮生长因子 基因突变 

分 类 号：R734.2[医药卫生—肿瘤] R730.54[医药卫生—临床医学]