Ma L, Lü J L, Li K, Wang J H, Yang X J, Li X, Zhang H, Zhang Q, Qin N, Zhang S C
Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.
Zhonghua Yi Xue Za Zhi. 2018 Aug 7;98(29):2336-2340. doi: 10.3760/cma.j.issn.0376-2491.2018.29.012.
To determine the clinical value of droplet digital polymerase chain reaction (ddPCR) method to detect plasma circulating tumor DNA (ctDNA) epidermal growth factor receptor (EGFR) mutations in advanced pulmonary adenocarcinoma. One hundred and thirty six patients with advanced pulmonary adenocarcinoma diagnosed in the Beijing Chest Hospital were collected from May 2015 to April 2017 for initial treatment. EGFR gene mutation in the plasma ctDNA was detected by both ddPCR and amplification refractory mutation system (ARMS) assays. EGFR gene mutation in the tumor tissue was detected by ARMS assay. Patients with EGFR sensitive mutations received first-line oral treatment with EGFR tyrosine kinase inhibitor (EGFR-TKI) drugs. The Kaplan-Meier survival analysis was used to compared the progression-free survival (PFS) in EGFR gene mutated patients detected with different methods. Total of 111 samples (81.6%) were detected with EGFR gene mutations in 136 tumor tissue samples. In the 111 samples, 48 samples were found with exon21 L858R mutation (48/111, 43.2%), 59 samples were found with exon19 deletion mutations (59/111, 53.2%), and 4 cases were found with other mutations (4/111, 3.6%). Using tumor specimens as the gold standard, the sensitivity, specificity, and concordance rate of ARMS assay were 58.6%, 96.0%, and 65.4%, respectively; and those in ddPCR assay were 79.3%, 100%, and 83.1%, respectively; the coincidence rate was 83.1% (=0.685, <0.001). Kaplan-Meier survival analysis showed that patients with EGFR gene mutation detected by both ddPCR and ARMS methods had shortest PFS when compared with those in patients detected positive with a single method of ddPCR or ARMS assay (11.6 moths vs 14.8 months, χ(2)=2.517, =0.026). ddPCR is a reliable technology with high sensitivity and high specificity to detect EGFR gene mutations in plasma ctDNA in patients with advanced pulmonary adenocarcinoma. Plasma EGFR gene mutation may predict the efficacy of EGFR-TKI drugs.
探讨液滴数字聚合酶链反应（ddPCR）法检测晚期肺腺癌患者血浆循环肿瘤DNA（ctDNA）表皮生长因子受体（EGFR）基因突变的临床价值。收集2015年5月至2017年4月在北京胸科医院确诊的136例晚期肺腺癌初治患者。采用ddPCR和扩增阻滞突变系统（ARMS）检测血浆ctDNA中的EGFR基因突变，采用ARMS检测肿瘤组织中的EGFR基因突变。EGFR敏感突变患者接受一线口服EGFR酪氨酸激酶抑制剂（EGFR-TKI）治疗。采用Kaplan-Meier生存分析比较不同方法检测到的EGFR基因突变患者的无进展生存期（PFS）。136例肿瘤组织样本中，共检测出111例（81.6%）存在EGFR基因突变。在这111例样本中，48例（48/111，43.2%）检测到外显子21 L858R突变，59例（59/111，53.2%）检测到外显子19缺失突变，4例（4/111，3.6%）检测到其他突变。以肿瘤标本为金标准，ARMS检测的敏感性、特异性和符合率分别为58.6%、96.0%和65.4%；ddPCR检测的敏感性、特异性和符合率分别为79.3%、100%和83.1%；符合率为83.1%（=0.685，<0.001）。Kaplan-Meier生存分析显示，与ddPCR或ARMS单一方法检测为阳性的患者相比，ddPCR和ARMS两种方法均检测到EGFR基因突变的患者PFS最短（11.6个月vs 14.8个月，χ(2)=2.517，=0.026）。ddPCR是一种可靠的技术，对检测晚期肺腺癌患者血浆ctDNA中的EGFR基因突变具有高敏感性和高特异性。血浆EGFR基因突变可能预测EGFR-TKI药物的疗效。
