采用微滴式数字PCR技术检测血浆EGFR基因突变状态在晚期非小细胞肺癌患者EGFR-TKI疗效评估中的价值

Predictive value of EGFR mutation detection in plasma by droplet digital PCR for the EGFR-TKI efficacy in advanced non-small cell lung cancer

目的探讨采用微滴式数字PCR技术检测晚期非小细胞肺癌患者血浆EGFR突变状态的可行性,及检测结果与接受埃克替尼疗效的相关性。方法分别采用AMRS法检测肿瘤组织样本,dPCR检测配对的血浆样本筛查晚期非小细胞肺癌患者(ⅢB/Ⅳ期)258例的EGFR表达状态,以肿瘤组织中的EGFR突变状态检测为对照,计算ddPCR法检测血浆EGFR突变状态的灵敏度、特异度、一致率。对于组织检测阳性和(或)血浆检测阳性的晚期NSCLC患者均给予埃克替尼靶向治疗。结果以配对的肿瘤组织EGFR突变检测结果为对照,ddPCR法检测血浆EGFR突变的灵敏度、特异度及一致率分别为66.7%,98.5%,83.8%。123例患者组织检测阳性和(或)血浆检测阳性,接受埃克替尼治疗,其中组织AMRS法检测阳性且血浆ddPCR检测阳性为A组(80例);组织AMRS检测阳性而血浆ddPCR检测阴性为B组(41例);组织AMRS检测阴性而血浆ddPCR检测阳性为C组(2例)。3组患者的DCR、ORR、PFS比较差异均无统计学意义(P=0.118,0.158,0.076)。结论 ddPCR法检测晚期NSCLC血浆中EGFR基因突变方法灵敏,取材方便;应用检测结果指导临床EGFR-TKIs治疗疗效与组织学检测结果比较差异无统计学意义,提示该方法预测疗效有良好的临床应用前景。

Objective To explore the feasibility of using droplet digital PCR to detect EGFR mutation in plasma of patients with advanced nonsmall cell lung cancer and the correlation between the EGFR mutation status and TKI response in NSCLC. Methods EGFR mutations in the tumor tissues and matched plasma samples from 258 advanced NSCLC patients were assessed using amplification refractory mutation system(AMRS)and droplet digital PCR(ddPCR). The sensitivity, specificity and consistency of EGFR mutations in plasma detected by ddPCR were calculated by taking the EGFR mutations in tumor tissues as the control group. Ektinib was given to patients carried EGFR sensitive mutations in tissue by AMRS and/or plasma by ddPCR. Results The sensitivity,specificity and consistency of EGFR mutations in plasma detected y ddPCR was 66.7%, 98.5%, 83.8%.123 patients carried EGFR sensitive mutations in tissue by AMRS and/or plasma by ddPCR received Ektinib therapy, including 80, 41, 2 in groups A(tumor tissue positive and plasma positive), B(tumor tissue positive and plasma negative) and C(tumor tissue negative and plasma positive). The DCR, ORR and median PFS of those receiving Ektinib across the three groups were similar(P=0.118, 0.158, 0.076, respectively). Conclusions EGFR mutation detected by ddPCR in plasma of patients with advanced NSCLC is highly sensitive. The results are consistent the clinical evaluation results of EGFR-TKI. It’s therefore promising in predicting treatment effectiveness.