198例手术切除的非小细胞肺癌患者应用ARMS法检测血浆表皮生长因子受体突变  

Detecting Plasma Epidermal Growth Factor Receptor Mutations of 198 Patients with Surgically Resected Non-small Cell Lung Cancer by Amplification Refractory Mutation System

作　　者：郭凯[1] 闫小龙[1] 张志培[1] 韩璐[2] 范亮波[1] 同李平[1] 张勇[1] 李小飞[1] 

机构地区：[1]第四军医大学唐都医院胸腔外科,西安710038 [2]第四军医大学西京医院超声科,西安710032

出　　处：《中国胸心血管外科临床杂志》2016年第6期602-607,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

摘　　要：目的探讨血浆表皮生长因子受体（EGFR）突变检测对早期非小细胞肺癌（NSCLC）基因诊断及预测NSCLC患者生存预后的价值。方法收集2014年2月至2015年6月唐都医院198例经扩增受阻突变体系（amplification refractory mutation system,ARMS）法检测手术切除组织EGFR突变为阳性的Ⅰ~Ⅳ期NSCLC患者术前全血。提取血浆cf DNA,实时定量荧光PCR对血浆进行EGFR突变检测,紫外分光光度法测定血浆cf DNA浓度。对ⅢA期患者进行术后随访观察,采用Kaplan-Meire法进行生存分析。结果血浆EGFR突变检测总敏感性为17.2%（34/198）。敏感性与TNM分期正相关,与肿瘤分化程度负相关。ⅢA期敏感性为33.3%,显著高于Ⅰ_A期1.6%（P=0.000）和Ⅰ_B期7.9%（P=0.004）。低分化癌敏感性为36.8%,显著高于高分化癌0.0（P=0.000）和中分化癌15.7%（P=0.010）。cf DNA浓度与患者特征无相关性。生存分析显示血浆EGFR突变检测是预测ⅢA期患者术后生存的重要因素（P=0.014）。结论目前血浆EGFR突变不能完全代替组织对早期NSCLC进行检测。但Ⅲ_A期及低分化癌血浆EGFR突变检测敏感性显著升高,因此对不能取到肿瘤组织的NSCLC患者,特别是低分化癌和ⅢA期患者推荐血浆检测EGFR突变及动态监控。血浆EGFR检测对局部进展期NSCLC患者的生存预后有预测价值。Objective To reveal the true value of plasma detection of epidermal growth factor receptor（EGFR） mutation for early-stage non-small cell lung cancer（NSCLC） gene diagnosis and to predict survival prognosis. Methods Tissue samples of positive EGFR mutations by using amplification refractory mutation system（ARMS） method were surgically resected from 198 patients with stage Ⅰ-Ⅳ NSCLC between February 2014 and June 2015 in Tangdu Hospital. Paired blood samples were collected before surgery. And the cellfree DNA（cf DNA） in plasma was extracted,plasma EGFR mutations were detected by real-time polymerase chain reaction（PCR）. Concentration of cf DNA was measured by ultraviolet spectrophotometry. Follow-up observation for stage ⅢA patients was put into force after surgery. Kaplan-Meire was used in survival analysis. Results The sensitivity of EGFR mutation for the 198 paired tissues and plasma samples was 17.2%.The sensitivity was positively correlated with TNM stage and negatively correlated with tumor differentiation. The sensitivity of sage ⅢA was 33.3%,significantly higher than that of the patients at stage ⅠA（1.6%,P=0.000） and stageⅠB（7.9%,P=0.004）. The sensitivity of poor differentiation was 36.8%,significantly higher than that of high differentiation（0.0%,P=0.000） and moderate differentiation（15.7%,P=0.010）. There was no correlation between plasma cf DNA concentration and patient characteristics. Survival analysis showed that plasma detection was a vital factor for predicting postoperative survival prognosis of stage Ⅲ_A patients（P=0.014）. Conclusion Tissue samples cannot be replaced by plasma samples for epidermal growth factor receptor（EGFR） mutation test in early-stage NSCLC patients,currently. When the sensitivity increases dramatically in the plasma samples of stage ⅢA NSCLC and poor differentiation tumor,we recommend using plasma detection for gene diagnosis,dynamic monitoring of EGFR mutations in stage ⅢA or poorly differentiated tumors,especially

关 键 词：表皮生长因子受体(EGFR)突变 非小细胞肺癌 血浆 扩增受阻突变体系(ARMS) 靶向治疗 生存率 生存因素 

分 类 号：R734.2[医药卫生—肿瘤]