Abstract
ObjectivesMET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC.MethodsTwo independent investigators applied parallel search strategies with the terms “MET AND lung cancer”, “MET AND NSCLC”, “MET gene copy number AND prognosis” in PubMed through January 2014. We selected the studies that investigated the association of MET gene copy number with survival, in patients who received surgery.ResultsAmong 1096 titles that were identified in the initial search, we retrieved 9 studies on retrospective cohorts with adequate retrievable data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Out of those, 6 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. We calculated the I2 statistic to assess heterogeneity (I2 = 72%). MET gene copy number predicted worse overall survival when all studies were combined in a random effects model (HR = 1.78, 95% CI 1.22–2.60). When only the studies that had at least 50% of adenocarcinoma patients in their populations were included, the effect was significant (five studies, HR 1.55, 95% CI 1.23–1.94). This was not true when we included only the studies with no more than 50% of the patients having adenocarcinoma histology (four studies HR 2.18, 95% CI 0.97–4.90).ConclusionsHigher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC. This prognostic impact may be adenocarcinoma histology specific.
Highlights
Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer related death worldwide [1]
As clinical benefit from chemotherapy with platinum doublets has reached a plateau, it becomes evident that further identification of putative targets and the optimization of targeted therapy strategies holds the premise of improvement in clinical outcomes
The MET receptor has been characterized as a transmembrane receptor that is activated by the Hepatocyte Growth Factor (HGF)
Summary
Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer related death worldwide [1]. Current treatment for metastatic disease is largely dependent on companion analysis of tissue and consists of targeted biologic therapy when a driver mutation is present or conventional chemotherapy at the absence of a putative target [2,3,4]. The MET receptor leads to proliferation and inhibition of apoptosis with activation of downstream PI3K/AKT and ERK pathways [7,8] while it promotes metastasis via the STAT system of transcription factors [9,10]. Tivantinib, a tyrosine kinase inhibitor in combination with erlotinib was found to prolong progression free survival (PFS) when compared to erlotinib alone in a phase II study in patients with non-squamous NSCLC [11]. On the other hand the combination of erlotinib with onartuzumab, a MET-specific monoclonal antibody prolonged PFS and OS compared with erlotinib alone in patients with METpositive NSCLC [12]
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