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

BACKGROUND: The 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. METHODS: PubMed, 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. RESULTS: Eighteen 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. CONCLUSIONS: Increased 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.