本文關(guān)鍵詞： 肺腺癌 表皮生長因子受體 循環(huán)腫瘤DNA 液體活檢 微滴數(shù)字PCR　出處：《重慶醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景及目的表皮生長因子受體酪氨酸激酶抑制劑(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)為表皮生長因子受體(epidermal growth factor receptor,EGFR)突變的非小細(xì)胞肺癌(non-small-cell lung cancer,NSCLC)患者帶來顯著的生存和生活質(zhì)量獲益,成為其不可或缺的治療方式。EGFR突變檢測因而成為晚期NSCLC治療選擇及預(yù)后判斷的一個重要手段�；谘h(huán)腫瘤DNA(circulating tumor DNA,ctDNA)的液體活檢作為一種無創(chuàng)、勻質(zhì)、可動態(tài)監(jiān)測的基因檢測手段近年來發(fā)展迅速,但其較高的假陰性率阻礙了其應(yīng)用。本研究旨在探討一天內(nèi)不同采血時間是否影響晚期肺腺癌患者外周血EGFR突變的檢測結(jié)果,并定量分析ctDNA中EGFR突變豐度與EGFR-TKIs治療臨床獲益的相關(guān)性。方法納入基線組織標(biāo)本及血標(biāo)本均為EGFR突變陽性的晚期初治肺腺癌患者,前瞻性收集患者同一天3個時間點(diǎn)(8:00,11:00及14:00)的外周血標(biāo)本,采用微滴數(shù)字PCR(droplet digital PCR,ddPCR)進(jìn)行定量分析。所有患者均接受一線吉非替尼治療,其療效參照實(shí)體瘤的療效評價標(biāo)準(zhǔn)(Response Evaluation Criteria in Solid Tumors,RECIST)1.1標(biāo)準(zhǔn)進(jìn)行評價。結(jié)果共22例IV期肺腺癌患者被納入至本研究。在所收集到的66份血液標(biāo)本中,中位EGFR突變豐度為7.13%(波動范圍0至35.09%),其中,6份血標(biāo)本EGFR突變豐度低于1.0%,1份血標(biāo)本EGFR突變?yōu)橐吧�。結(jié)果提示EGFR突變豐度在不同時間點(diǎn)存在動態(tài)波動,然而其差值并無統(tǒng)計(jì)學(xué)意義(P=0.557)。根據(jù)EGFR突變豐度的高低,將患者分為高頻突變患者(EGFR突變豐度6.76%)和低頻突變患者(EGFR突變豐度≤6.76%),結(jié)果顯示前者吉非替尼治療療效較好(P=0.024)。結(jié)論ctDNA的釋放可能是一個時間異質(zhì)性的過程。不同采血時間對EGFR突變檢測結(jié)果沒有影響。ctDNA中的EGFR相對豐度可以預(yù)測晚期肺腺癌患者EGFR-TKIs療效。
[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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