Cancer Research Institute of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University (Yunnan cancer Hospital), Kunming, 650118, P.R. China.
International Joint Laboratory on High Altitude Regional Cancer of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, P.R. China.
Sci Rep. 2018 Oct 18;8(1):15426. doi: 10.1038/s41598-018-33816-x.
To explore the effect of epidermal growth factor receptor (EGFR) T790M mutation status on non-small cell lung cancer (NSCLC) in Yunnan province of southwestern China. First, this study used the super amplification refractory mutation system (Super ARMS) polymerase chain reaction (PCR) and Droplet Digital PCR (dd PCR) to evaluate the T790M gene mutation, in plasmatic ctDNA samples from 212 cases of NSCLC. The association between T790M mutations and clinical parameters were further explored. Next, to investigate the mechanism of drug resistance that resulted from T790M mutation, subgroup analyses according to duration of medicine (EGFR-TKIs) were carried out. Finally, we also evaluate the effectiveness of blood-based circulating tumor DNA (ctDNA) on detecting the T790M mutation by calculating Super ARMS's detection efficiency. We found that the T790M mutation rate was 8.4% (18/212) in overall patients. The T790M mutation was more frequent in patients with brain metastasis 30.0% (12/40) (p < 0.01). We found that post-TKI samples 42.8% (15/35) were associated with a higher T790M mutation rate (p < 0.01). Subgroup analysis showed that the duration of TKI therapy for 6 to 10 months 66.6% (8/12) (p < 0.01) and >10 months 75.0% (9/12) (p < 0.01) were also associated with a higher T790M mutation rate. Super ARMS's sensitivity, specificity, PPV, NPV, and accuracy were 100.0%, 99.4%, 94.7%, 100.0%, and 99.5% respectively. Generally, the EGFR-T790M mutation was more common in NSCLC patients with brain metastasis and those who received TKI therapy for more than 6 months. Moreover, Super ARMS is a sensitive, efficient, and practical clinic method for dynamically monitoring T790M mutation status and effectively guiding clinic treatment.
探讨表皮生长因子受体(EGFR)T790M 突变状态对中国西南部云南省非小细胞肺癌(NSCLC)的影响。首先,本研究采用超级扩增难治性突变系统(Super ARMS)聚合酶链反应(PCR)和液滴数字 PCR(ddPCR)对 212 例 NSCLC 患者的血浆 ctDNA 样本中的 T790M 基因突变进行评估,并进一步探讨 T790M 突变与临床参数的关系。接下来,为了研究 T790M 突变导致耐药的机制,根据药物(EGFR-TKIs)的使用时间进行亚组分析。最后,我们还通过计算 Super ARMS 的检测效率来评估基于血液的循环肿瘤 DNA(ctDNA)检测 T790M 突变的有效性。结果:在所有患者中,T790M 突变率为 8.4%(18/212)。T790M 突变在有脑转移的患者中更为常见,占 30.0%(12/40)(p<0.01)。我们发现,TKI 治疗后的样本中,42.8%(15/35)的 T790M 突变率较高(p<0.01)。亚组分析显示,TKI 治疗时间为 6 至 10 个月的患者中有 66.6%(8/12)(p<0.01)和>10 个月的患者中有 75.0%(9/12)(p<0.01)的 T790M 突变率也较高。Super ARMS 的灵敏度、特异性、PPV、NPV 和准确性分别为 100.0%、99.4%、94.7%、100.0%和 99.5%。一般来说,EGFR-T790M 突变在有脑转移和 TKI 治疗超过 6 个月的 NSCLC 患者中更为常见。此外,Super ARMS 是一种敏感、高效、实用的临床方法,可用于动态监测 T790M 突变状态,并有效指导临床治疗。