Super-ARMS法在检测非小细胞肺癌EGFR基因突变中的应用分析
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摘要
目的本研究通过对超级突变扩增阻滞系统(Super-ARMS)法与突变扩增阻滞系统法(ARMS)检测晚期非小细胞肺癌患者表皮生长因子受体(EGFR)基因突变的比较分析,探索Super-ARMS法的临床应用价值。方法收集111例晚期非小细胞肺癌患者外周血标本,提取血浆游离DNA后,分别采用Super-ARMS法及ARMS法进行EGFR基因突变检测,同时对53例配对的石蜡组织切片采用ARMS法进行EGFR基因突变检测。结果 111例标本中,Super-ARMS法检测EGFR基因突变率为50.5%(56/111),ARMS法检测EGFR基因突变率为46.9%(52/111);Super-ARMS法检测出T790M单突变3例,双突变5例,ARMS法则未检测出相关突变,两者比较差异有统计学意义(χ~2=8.023,P<0.01);两种方法检测EGFR基因突变一致率达87.4%(97/111),一致性检验显示Kappa系数为0.748(95%CI:0.624～0.871,P<0.001);通过检测53例配对组织样本的EGFR基因突变情况显示,与组织ARMS法比较,Super-ARMS法检测的敏感性、特异性和准确性分别为70.8%(17/24)、89.7%(26/29)和81.1%(43/53)。结论 Super-ARMS法与ARMS法检测EGFR基因突变结果一致性较高,Super-ARMS法检测T790M突变的敏感性明显优于ARMS法。
Objective To compare the concordance of epidermal growth factor receptor(EGFR) mutations detected in terminal non-small cell lung cancer( NSCLC) by Super Amplification Refractory Mutation System(Super-ARMS) and Amplification Refractory Mutation System(ARMS), and investigate the clinical application value of Super-ARMS.Methods A total of 111 whole blood samples were collected from patients with advanced stage NSCLC. EGFR genes were detected by Super-ARMS and ARMS after plasma free DNA was extracted. EGFR mutations in 53 cases of paired tissue setions were detected by ARMS simultaneously. Results The mutation rates of EGFR detected by Super-ARMS and ARMS were 50.5%(56/111) and 46.9%(52/111), respectively. 3 cases of T790M mutation and 5 cases of double mutation were detected by Super-ARMS, none of these mutations were found by ARMS. The difference was statistically significant( X~2 =8.023,P<0.01). The concordance rate by two methods was 87.4%( 97/111).The Kappa value was 0.748(95% CI: 0.624-0.871, P<0.001). Compared with the results of EGFR detection in 53 cases of tissue sections, the sensitivity, specificity and accuracy of Super-ARMS were 70.8%( 17/24), 89.7%(26/29) and 81.1%(43/53), respectively. Conclusions The Super-ARMS showed high concordance in detecting EGFR mutations when compare with ARMS. The sensitivity of SuperARMS to detect T790M mutation was much better than that of ARMS.
Objective To compare the concordance of epidermal growth factor receptor(EGFR) mutations detected in terminal non-small cell lung cancer( NSCLC) by Super Amplification Refractory Mutation System(Super-ARMS) and Amplification Refractory Mutation System(ARMS), and investigate the clinical application value of Super-ARMS.Methods A total of 111 whole blood samples were collected from patients with advanced stage NSCLC. EGFR genes were detected by Super-ARMS and ARMS after plasma free DNA was extracted. EGFR mutations in 53 cases of paired tissue setions were detected by ARMS simultaneously. Results The mutation rates of EGFR detected by Super-ARMS and ARMS were 50.5%(56/111) and 46.9%(52/111), respectively. 3 cases of T790M mutation and 5 cases of double mutation were detected by Super-ARMS, none of these mutations were found by ARMS. The difference was statistically significant( X~2 =8.023,P<0.01). The concordance rate by two methods was 87.4%( 97/111).The Kappa value was 0.748(95% CI: 0.624-0.871, P<0.001). Compared with the results of EGFR detection in 53 cases of tissue sections, the sensitivity, specificity and accuracy of Super-ARMS were 70.8%( 17/24), 89.7%(26/29) and 81.1%(43/53), respectively. Conclusions The Super-ARMS showed high concordance in detecting EGFR mutations when compare with ARMS. The sensitivity of SuperARMS to detect T790M mutation was much better than that of ARMS.
引文
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[9]Cui S,Ye L,Wang H,et al.Use of SuperARMS EGFR mutation detection kit to detect EGFR in plasma cell-free DNA of patients with lung adenocarcinoma.clinical lung cancer[J].Clin Lung Cancer,2018,19(3):e313-e322.
[10]Kumarakulasinghe NB,Van ZN,Soo RA.Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer(NSCLC)[J].Respirology,2015,20(3):370-378.
[11]Li Y,Xu H,Su S,et al.Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma[J].PloS One,2017,12(8):e0183331.
[12]中国非小细胞肺癌患者EGFR T790M基因突变检测专家共识[J].中华医学杂志,2018,98(32):2544-2551.
[13]Feng WN,Gu WQ,Zhao N,et al.Comparison of the SuperARMSand droplet digital PCR for detecting EGFR mutation in ctDNAfrom NSCLC patients[J].Transl Oncol,2018,11(2):542-545.
[2]Lin CC,Yang JC.Optimal management of patiens with non-small cell lung cancer and epidermal growth factor receptor mutations[J].Drugs,2011,71(1):79-88.
[3]李歆,李志阳,徐韫健,等.非小细胞肺癌患者血浆EGFR基因突变的检测[J].热带医学杂志,2017,17(9):1144-1147.
[4]梁颖,林勇平,徐韫健,等.非小细胞肺癌EGFR基因突变的异质性[J].热带医学杂志,2015,15(12):1590-1594.
[5]非小细胞肺癌血液EGFR基因突变检测中国专家组.非小细胞肺癌血液EGFR基因突变中国专家共识[J].中华医学杂志,2015,46(95):3721-3726.
[6]Gridelli C,Ciardicllo F,Gallo C,et al.First-line crlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer:the TORCH randomized trial[J].J Clin Oncol,2012,30(24):3002-3011.
[7]Engelman JA,Janne PA.Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in nonsmall cell lung cancer[J].Clin Cancer Res,(2008,14(10):2895-2899.
[8]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[9]Cui S,Ye L,Wang H,et al.Use of SuperARMS EGFR mutation detection kit to detect EGFR in plasma cell-free DNA of patients with lung adenocarcinoma.clinical lung cancer[J].Clin Lung Cancer,2018,19(3):e313-e322.
[10]Kumarakulasinghe NB,Van ZN,Soo RA.Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer(NSCLC)[J].Respirology,2015,20(3):370-378.
[11]Li Y,Xu H,Su S,et al.Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma[J].PloS One,2017,12(8):e0183331.
[12]中国非小细胞肺癌患者EGFR T790M基因突变检测专家共识[J].中华医学杂志,2018,98(32):2544-2551.
[13]Feng WN,Gu WQ,Zhao N,et al.Comparison of the SuperARMSand droplet digital PCR for detecting EGFR mutation in ctDNAfrom NSCLC patients[J].Transl Oncol,2018,11(2):542-545.