Zhang Xinxin, Chang Ning, Yang Guohua, Zhang Yong, Ye Mingxiang, Cao Jing, Xiong Jie, Han Zhiping, Wu Shuo, Shang Lei, Zhang Jian
Department of Pulmonary Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Research and Development Department, GenoSaber Biotech Co. Ltd., Shanghai, China.
Oncotarget. 2017 Dec 6;8(67):112014-112023. doi: 10.18632/oncotarget.22997. eCollection 2017 Dec 19.
In this study, we introduce a novel amplification refractory mutation system (ARMS)-based assay, namely ARMS-Plus, for the detection of epidermal growth factor receptor (EGFR) mutations in plasma samples. We evaluated the performance of ARMS-Plus in comparison with droplet digital PCR (ddPCR) and assessed the significance of plasma EGFR mutations in predicting efficacy of EGFR-tyrosine kinase inhibitor (TKI) regimen. A total of 122 advanced non-small cell lung cancer (NSCLC) patients were enrolled in this study. The tumor tissue samples from these patients were evaluated by conventional ARMS PCR method to confirm their EGFR mutation status. For the 116 plasma samples analyzed by ARMS-Plus, the sensitivity, specificity, and concordance rate were 77.27% (34/44), 97.22% (70/72), and 89.66% (104/116; κ=0.77, <0.0001), respectively. Among the 71 plasma samples analyzed by both ARMS-Plus and ddPCR, ARMS-Plus showed a higher sensitivity than ddPCR (83.33% versus 70.83%). The presence of EGFR activating mutations in plasma was not associated with the response to EGFR-TKI, although further validation with a larger cohort is required to confirm the correlation. Collectively, the performance of ARMS-Plus and ddPCR are comparable. ARMS-Plus could be a potential alternative to tissue genotyping for the detection of plasma EGFR mutations in NSCLC patients.
在本研究中，我们引入了一种基于新型扩增阻滞突变系统（ARMS）的检测方法，即ARMS-Plus，用于检测血浆样本中的表皮生长因子受体（EGFR）突变。我们将ARMS-Plus的性能与液滴数字PCR（ddPCR）进行了比较，并评估了血浆EGFR突变在预测EGFR酪氨酸激酶抑制剂（TKI）方案疗效中的意义。本研究共纳入了122例晚期非小细胞肺癌（NSCLC）患者。通过传统ARMS PCR方法对这些患者的肿瘤组织样本进行评估，以确认其EGFR突变状态。对于采用ARMS-Plus分析的116份血浆样本，其灵敏度、特异性和符合率分别为77.27%（34/44）、97.22%（70/72）和89.66%（104/116；κ=0.77，<0.0001）。在同时采用ARMS-Plus和ddPCR分析的71份血浆样本中，ARMS-Plus的灵敏度高于ddPCR（83.33%对70.83%）。血浆中EGFR激活突变的存在与对EGFR-TKI的反应无关，尽管需要更大样本量的队列进一步验证来确认这种相关性。总体而言，ARMS-Plus和ddPCR的性能相当。ARMS-Plus可能是检测NSCLC患者血浆EGFR突变的组织基因分型的一种潜在替代方法。
