Lung Cancer Center, Konkuk University Medical Center, Seoul, Republic of Korea.
Department of Pathology, Konkuk University Medical Center, Seoul, Republic of Korea.
Mol Cancer. 2018 Jan 27;17(1):15. doi: 10.1186/s12943-018-0772-6.
Tumor cells shed an abundance of extracellular vesicles (EVs) to body fluids containing bioactive molecules including DNA, RNA, and protein. Investigations in the field of tumor-derived EVs open a new horizon in understanding cancer biology and its potential as cancer biomarkers as well as platforms for personalized medicine. This study demonstrates that successfully isolated EVs from plasma and bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC) patients contain DNA that can be used for EGFR genotyping through liquid biopsy. In both plasma and BALF samples, liquid biopsy results using EV DNA show higher accordance with conventional tissue biopsy compared to the liquid biopsy of cfDNA. Especially, liquid biopsy with BALF EV DNA is tissue-specific and extremely sensitive compared to using cfDNA. Furthermore, use of BALF EV DNA also demonstrates higher efficiency in comparison to tissue rebiopsy for detecting p.T790 M mutation in the patients who developed resistance to EGFR-TKIs. These finding demonstrate possibility of liquid biopsy using EV DNA potentially replacing the current diagnostic methods for more accurate, cheaper, and faster results.
肿瘤细胞会向体液中释放大量的细胞外囊泡（EVs），其中包含有生物活性的分子，包括 DNA、RNA 和蛋白质。对肿瘤衍生 EVs 的研究为理解癌症生物学及其作为癌症生物标志物的潜力以及个性化医疗平台开辟了新的视野。本研究表明，成功地从非小细胞肺癌（NSCLC）患者的血浆和支气管肺泡灌洗液（BALF）中分离出的 EV 含有可用于通过液体活检进行 EGFR 基因分型的 DNA。在血浆和 BALF 样本中，与 cfDNA 的液体活检相比，使用 EV DNA 的液体活检结果与传统组织活检具有更高的一致性。特别是与 cfDNA 相比，BALF EV DNA 的液体活检具有组织特异性和极高的灵敏度。此外，与组织再次活检相比，使用 BALF EV DNA 检测对 EGFR-TKIs 产生耐药性的患者中 p.T790M 突变的效率也更高。这些发现表明，使用 EV DNA 进行液体活检有可能替代当前的诊断方法，以获得更准确、更便宜、更快的结果。
