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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 MET 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 MET copy number (CN) in cancer patients (r = 0.57, p &lt, 10&minus, 10) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch&reg, and Parsortix systems and monitored patients under anti-EGFR treatment (n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET 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 MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.

The alterations of MET have been detected in non-small-cell lung cancer (NSCLC). However, the prognostic impact of MET gene copy number gain (CNG) has not been consistent among studies. We performed this meta-analysis to evaluate the prognostic value of high MET CNG in patients with NSCLC. A systematic computerized search of the electronic databases including PubMed, EMBASE, Google scholar, and Cochrane Library (up to November 2017) was carried out. From twenty-one studies, 7,647 patients were included in the pooled analysis of hazard ratios (HRs) with 95% confidence intervals (CIs) for disease-free survival or overall survival. Compared with patients with NSCLC showing low MET CNG, those with tumors harboring high MET CNG showed significantly worse survival (HR = 1.45, 95% CI: 1.16-1.80, p = 0.001). Subgroup analyses showed that high MET CNG significantly correlated with a poor prognosis especially in patients with adenocarcinoma (HR = 1.41, 95% CI: 1.11-1.79, p = 0.005) and Asian populations (HR = 1.58, 95% CI: 1.32-1.88, p < 0.00001). In conclusion, this meta-analysis indicates that high MET CNG is an adverse prognostic factor in patients with NSCLC. Subgroup analyses suggest that high MET CNG is associated with a worse prognosis, especially in patients with adenocarcinoma and Asian populations. However, large prospective studies using standardized methods based on the homogeneous populations are warranted to validate the prognostic value of MET amplification in patients with NSCLC.