Prognostic Value of MET Gene Copy Number and Protein Expression in Patients with Surgically Resected Non-Small Cell Lung Cancer: A Meta-Analysis of Published Literatures

Abstract

BackgroundThe prognostic value of the copy number (GCN) and protein expression of the mesenchymal-epithelial transition (MET) gene for survival of patients with non-small cell lung cancer (NSCLC) remains controversial. This study aims to comprehensively and quantitatively asses the suitability of MET GCN and protein expression to predict patients' survival.MethodsPubMed, Embase, Web of Science and Google Scholar were searched for articles comparing overall survival in patients with high MET GCN or protein expression with those with low level. Pooled hazard ratio (HR) and 95% confidence intervals (CIs) were calculated using the random and the fixed-effects models. Subgroup and sensitivity analyses were also performed.ResultsEighteen eligible studies enrolling 5,516 patients were identified. Pooled analyses revealed that high MET GCN or protein expression was associated with poor overall survival (OS) (GCN: HR = 1.90, 95% CI 1.35–2.68, p<0.001; protein expression: HR = 1.52, 95% CI 1.08–2.15, p = 0.017). In Asian populations (GCN: HR = 2.22, 95% CI 1.46–3.38, p<0.001; protein expression: HR = 1.89, 95% CI 1.34–2.68, p<0.001), but not in the non-Asian subset. For adenocarcinoma, high MET GCN or protein expression indicated decreased OS (GCN: HR = 1.49, 95% CI 1.05–2.10, p = 0.025; protein expression: HR = 1.69, 95% CI 1.31–2.19, p<0.001). Results were similar for multivariate analysis (GCN: HR = 1.61, 95% CI 1.15–2.25, p = 0.005; protein expression: HR = 2.18, 95% CI 1.60–2.97, p<0.001). The results of the sensitivity analysis were not materially altered and did not draw different conclusions.ConclusionsIncreased MET GCN or protein expression was significantly associated with poorer survival in patients with surgically resected NSCLC; this information could potentially further stratify patients in clinical treatment.

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

“…This statement was evidence based and supported by 7 studies, 107e113 comprising 1 MA, 107 1 phase II randomized controlled trial, 109 1 PCS, 110 and 4 RCSs. 108,111e113 All included studies were assessed for quality and none were found to have methodologic flaws that would raise concerns about the studies' finding (SDC Table 18).…”

“…Despite the reported association of the MET gene amplification and high protein expression as a poor prognostic marker 107,125 and recent reports that patients with MET amplification or MET exon 14 mutation are sensitive to crizotinib in some cases, there is as yet no approved targeted therapy to treat patients whose tumor harbor these MET genomic aberrations. 126e130 In this context, a routine stand-alone testing for these MET genomic aberrations or HGFR protein level is not indicated outside a clinical trial.…”

“…137,138 An MA has found that MET expression by IHC in NSCLC is a negative prognostic factor in patients with surgically resected NSCLC. 107 A frequently used commercially available antibody, particularly in clinical trials, is the CONFIRM anti-total MET (SP44) rabbit monoclonal primary antibody (Ventana Medical Systems, Tucson, Arizona) directed against a membranous and cytoplasmic epitope of MET. 109 At the time of publication, it remains unclear whether total MET or phosphoMET protein overexpression represents a reliable indicator of MET activation.…”

Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Study

“…In such group, excluding the cases with oncogene addiction (3 EGFR mutations and one ALK translocation), acquired MET amplification was observed in 7 out of 15 cases. These data differ from literature data and the discrepancy could reflect the highly conflicting results about MET positivity prevalence in NSCLC, ranging from 2% to 20%, probably due to different methods of analysis and criteria used for FISH scoring [21,22]. Cappuzzo et al [11], investigated a series of radically resected NSCLC and reported a MET amplification in approximately 11.1% of the cases.…”

Onartuzumab in lung cancer: the fall of Icarus?

“…In this population, c-MET overexpression can be found in 14-69% of patients [3] and de novo c-MET amplification in about 5% [4,5].…”