不同采血时间对晚期肺腺癌EGFR突变检测结果影响的分析研究

发布时间：2018-02-28 03:02

  本文关键词： 肺腺癌 表皮生长因子受体 循环肿瘤DNA 液体活检 微滴数字PCR　出处：《重庆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景及目的表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)为表皮生长因子受体(epidermal growth factor receptor,EGFR)突变的非小细胞肺癌(non-small-cell lung cancer,NSCLC)患者带来显著的生存和生活质量获益,成为其不可或缺的治疗方式。EGFR突变检测因而成为晚期NSCLC治疗选择及预后判断的一个重要手段。基于循环肿瘤DNA(circulating tumor DNA,ctDNA)的液体活检作为一种无创、匀质、可动态监测的基因检测手段近年来发展迅速,但其较高的假阴性率阻碍了其应用。本研究旨在探讨一天内不同采血时间是否影响晚期肺腺癌患者外周血EGFR突变的检测结果,并定量分析ctDNA中EGFR突变丰度与EGFR-TKIs治疗临床获益的相关性。方法纳入基线组织标本及血标本均为EGFR突变阳性的晚期初治肺腺癌患者,前瞻性收集患者同一天3个时间点(8:00,11:00及14:00)的外周血标本,采用微滴数字PCR(droplet digital PCR,ddPCR)进行定量分析。所有患者均接受一线吉非替尼治疗,其疗效参照实体瘤的疗效评价标准(Response Evaluation Criteria in Solid Tumors,RECIST)1.1标准进行评价。结果共22例IV期肺腺癌患者被纳入至本研究。在所收集到的66份血液标本中,中位EGFR突变丰度为7.13%(波动范围0至35.09%),其中,6份血标本EGFR突变丰度低于1.0%,1份血标本EGFR突变为野生型。结果提示EGFR突变丰度在不同时间点存在动态波动,然而其差值并无统计学意义(P=0.557)。根据EGFR突变丰度的高低,将患者分为高频突变患者(EGFR突变丰度6.76%)和低频突变患者(EGFR突变丰度≤6.76%),结果显示前者吉非替尼治疗疗效较好(P=0.024)。结论ctDNA的释放可能是一个时间异质性的过程。不同采血时间对EGFR突变检测结果没有影响。ctDNA中的EGFR相对丰度可以预测晚期肺腺癌患者EGFR-TKIs疗效。
[Abstract]:Background and objective epidermal growth factor receptor tyrosine kinase inhibitor, epidermal growth factor receptor tyrosine kinase inhibitor, EGFR-TKIs-epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) patients with non-small- cell lung cancer has significant benefits in survival and quality of life (QOL). As an indispensable therapeutic method, EGFR mutation detection has become an important method for the selection of treatment and prognosis of advanced NSCLC. Fluid biopsy based on circulating tumor DNA(circulating tumor DNA is a noninvasive, homogenous, noninvasive and homogenous. The method of dynamically monitoring gene detection has developed rapidly in recent years, but its high false negative rate hinders its application. This study was designed to investigate whether different blood sampling time in a day affects the detection results of EGFR mutation in peripheral blood of patients with advanced lung adenocarcinoma. The relationship between EGFR mutation abundance in ctDNA and the clinical benefit of EGFR-TKIs treatment was quantitatively analyzed. Methods the patients with advanced lung adenocarcinoma whose EGFR mutation was positive in baseline tissue and blood samples were included in this study. The peripheral blood samples of 8: 00, 11: 00 and 14: 00 on the same day were collected prospectively and analyzed quantitatively by PCR(droplet digital ddPCR. All the patients received first-line gifitinib therapy. The efficacy was evaluated according to response Evaluation Criteria in Solid tumor RECIST 1.1 criteria. Results A total of 22 patients with stage IV lung adenocarcinoma were included in this study. 66 blood samples were collected. The median EGFR mutation abundance was 7.13 (range 0 to 35.09). The EGFR mutation abundance of 6 blood samples was less than 1.0% and 1 of them was wild type. The results suggested that the EGFR mutation abundance fluctuated dynamically at different time points. However, the difference was not statistically significant (P < 0. 557). According to the abundance of EGFR mutation, The patients were divided into high frequency mutation patients with high frequency mutation and low frequency mutation patients with EGFR mutation abundance 鈮，

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