Park Juhee, Lee Chaeeun, Eom Jung Seop, Kim Mi-Hyun, Cho Yoon-Kyoung
Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan 44919, Korea.
Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea.
Cancers (Basel). 2020 Sep 30;12(10):2822. doi: 10.3390/cancers12102822.
The detection of epidermal growth factor receptor () mutation, based on tissue biopsy samples, provides a valuable guideline for the prognosis and precision medicine in patients with lung cancer. In this study, we aimed to examine minimally invasive bronchial washing (BW)-derived extracellular vesicles (EVs) for mutation analysis in patients with lung cancer. A lab-on-a-disc equipped with a filter with 20-nm pore diameter, Exo-Disc, was used to enrich EVs in BW samples. The overall detection sensitivity of mutations in 55 BW-derived samples was 89.7% and 31.0% for EV-derived DNA (EV-DNA) and EV-excluded cell free-DNA (EV-X-cfDNA), respectively, with 100% specificity. The detection rate of T790M in 13 matched samples was 61.5%, 10.0%, and 30.8% from BW-derived EV-DNA, plasma-derived cfDNA, and tissue samples, respectively. The acquisition of T790M resistance mutation was detected earlier in BW-derived EVs than plasma or tissue samples. The longitudinal analysis of BW-derived EVs showed excellent correlation with the disease progression measured by CT images. The mutations can be readily detected in BW-derived EVs, which demonstrates their clinical potential as a liquid-biopsy sample that may aid precise management, including assessment of the treatment response and drug resistance in patients with lung cancer.
基于组织活检样本检测表皮生长因子受体（）突变，为肺癌患者的预后和精准医学提供了有价值的指导。在本研究中，我们旨在检测微创支气管灌洗（BW）衍生的细胞外囊泡（EVs），用于肺癌患者的 突变分析。使用配备有孔径为20纳米过滤器的盘上实验室Exo-Disc来富集BW样本中的EVs。55个BW衍生样本中 突变的总体检测灵敏度，EV衍生DNA（EV-DNA）为89.7%，排除EV的游离DNA（EV-X-cfDNA）为31.0%，特异性均为100%。13个匹配样本中T790M的检测率，BW衍生的EV-DNA为61.5%，血浆衍生的cfDNA为10.0%，组织样本为30.8%。在BW衍生的EVs中比在血浆或组织样本中更早检测到T790M耐药突变。对BW衍生的EVs进行纵向分析显示，与CT图像测量的疾病进展具有良好的相关性。在BW衍生的EVs中可以很容易地检测到 突变，这证明了它们作为液体活检样本的临床潜力，可能有助于精准管理，包括评估肺癌患者的治疗反应和耐药性。
