摘要
目的探讨数字聚合酶链反应(droplet digital polymerase chain reaction,ddPCR)技术检测肺腺癌循环肿瘤DNA(circulating tumor DNA,ctDNA)中表皮生长因子受体(epidermal growth factor receptor,EGFR)突变的临床意义。方法采用ddPCR技术检测肺腺癌患者102例的ctDNA中EGFR突变即EGFR-L858R突变和EGFR-19del突变。分析ctDNA与患者临床参数的关系。绘制ROS曲线,评估ctDNA对患者预后和是否发生转移的预测作用。结果ddPCR技术检测ctDNA中EGFR突变评价EGFR突变状态的曲线下面积(area under the curve,AUC)为0.694,敏感度为40.2%,特异度为88.6%。与早期肺腺癌相比,晚期肺腺癌患者ctDNA中EGFR突变检测的AUC(0.837 vs.0.498)和敏感度(75.2%vs.10.2%)更高。肿瘤发生转移与ctDNA中EGFR突变丰度呈强的正相关性(r=0.510,P<0.001)。ctDNA阳性组的无进展生存期、总生存时间明显短于ctDNA阴性组(13.8个月vs.42.2个月,34.4个月vs.66.8个月,P<0.05),接受人表皮生长因子受体酪氨酸激酶抑制剂治疗的ctDNA阳性组无进展生存期短于ctDNA阴性组(12.0个月vs.24.0个月,P<0.05);此外,ctDNA阳性患者的总生存时间较阴性组缩短(34.4个月vs.66.8个月,P<0.05)。结论ddPCR技术可用于检测晚期肺腺癌患者中ctDNA中EGFR突变,ctDNA中EGFR阳性提示患者可能存在远处转移和预后差。
Objective To investigate the clinical significance of droplet digital polymerase chain reaction(ddPCR)in detecting epidermal growth factor receptor(EGFR)mutation in circulating tumor DNA(ctDNA)of lung adenocarcinoma.Methods The ddPCR was used to analyze EGFR mutation(EGFR-L858R and EGFR-19Del mutations)in plasma ctDNA in 102 patients with lung adenocarcinoma.The relationship between ctDNA and clinical parameters was analyzed.The ROS curves were drawn to evaluate the predictive effect of ctDNA on prognosis and metastasis of patients.Results The area under the ROC curve of ddPCR in detecting EGFR mutation in ctRNA for evaluation of EGFR mutation was 0.964,and the sensitivity and specificity were 40.2%and 88.6%respectively.Compared with early-stage lung adenocarcinoma,advanced-stage lung adenocarcinoma had higher AUC(0.837 vs.0.498)and sensitivity(75.2%vs.10.2%).Tumor metastasis and fractional abundance of ctDNA showed a strong correlation(r=0.51,P<0.001).There was a significantly shorter progression-free survival(PFS)and overall survival(OS)in the ctDNA-positive group than in the ctDNA-negative group(13.8 months vs.42.2 months,P<0.05,34.4 months vs.66.8 months,P<0.05).PFS of ctDNA-positive group treated with human epidermal growth factor receptor tyrosine kinase inhibitor was shorter than that of ctDNA-negative group(12.0 months vs.24.0 months,P<0.05).In addition,OS was shorter in ctDNA-positive patients than in ctDNA-negative patients(34.4 months vs.66.8 months,P<0.05).Conclusion DdPCR can be used to detect EGFR mutation in ctDNA of patients with advanced lung adenocarcinoma.EGFR mutation-positive lung adenocarcinoma in ctDNA indicates that patients may have distant metastasis and poor prognosis.
作者
汤涛
陈曦
陈铜兵
王辉
TANG Tao;CHEN Xi;CHEN Tong-bing;WANG Hui(Department of Pathology,the First People′s Hospital of Changzhou City,Jiangsu Province,Changzhou 213003,China)
出处
《河北医科大学学报》
CAS
2023年第2期224-229,共6页
Journal of Hebei Medical University
基金
常州市卫健委青年人才项目(QN202005)。
关键词
肺腺癌
循环肿瘤DNA
聚合酶链反应
adenocarcinoma of lung
circulating tumor DNA
polymerase chain reaction