Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain.
Department of Medical Oncology, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain.
Cells. 2020 Feb 24;9(2):522. doi: 10.3390/cells9020522.
MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and copy number (CN) in cancer patients ( = 0.57, <10) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch and Parsortix systems and monitored patients under anti-EGFR treatment ( = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET and the Overall Survival (OS) in head and neck cancer patients (P = 0.05; HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.
MET 改变可能提供一个潜在的生物标志物，用于评估受益于 MET 抑制剂治疗的患者。因此，本研究的目的是研究基于液体活检的策略在评估癌症患者 MET 改变中的应用。我们分析了 174 名癌症患者和 49 名健康对照者循环游离 DNA (cfDNA)中的扩增情况，并证明了该分析检测其在患者中改变的准确性。重要的是，在癌症患者中确定了 cfDNA 浓度与 拷贝数 (CN) 之间的显著相关性 (=0.57，<10)。此外，我们使用 CellSearch 和 Parsortix 系统评估了两种检测循环肿瘤细胞 (CTC) 中 MET 存在的方法，并在 30 名接受抗 EGFR 治疗的患者中结合 cfDNA 和 CTCs 分析进行了监测。这一随访为当患者对抗 EGFR 治疗产生耐药性时进行 CN 评估的潜力提供了证据，并表明 CTCs MET 的存在与头颈部癌症患者的总生存期 (OS) 之间存在显著关联 (P=0.05；HR=6.66)。总之，我们开发了特异性和非侵入性的检测方法来监测 cfDNA/CTCs 中的 MET 状态，并证明了血浆 CN 测定作为监测抗 EGFR 治疗耐药性出现的生物标志物的效用。
