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.
Highlights
Lung cancer continues to be the most common and deadly malignant cancers worldwide [1]
Studies meeting the following inclusion criteria were considered for this meta-analysis: (I) Clinical trials and prospective or retrospective cohort studies investigating the correlation of the mesenchymal-epithelial transition (MET) GCN and protein expression status with the overall survival (OS) of non-small cell lung cancer (NSCLC) patients; (II) Measurement methods, including fluorescent in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR), and immunohistochemistry (IHC); and (III) Findings providing sufficient information for the estimation of hazard ratios and 95% confidence intervals
As indicated in the search flow diagram (Figure 1), 18 studies were included in the meta-analysis [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,33,34]. 6 studies provided survival data for both MET GCN and protein expression are listed twice in Table 1 and Table 2 respectively [13,14,18,19,20,21]
Summary
Lung cancer continues to be the most common and deadly malignant cancers worldwide [1]. The MET gene, located at 7q21-q31, is a potential prognostic genetic marker, which encodes a receptor tyrosine kinase for the HGF/scatter factor (SF) [4]. Met-receptor tyrosine kinase is activated through phosphorylation and the cognate ligand HGF, leading to the activation of a number of downstream pathways, such as the phosphoinositide-3-kinase (PI3K), Ras-Rac/Rho, Ras mitogen-activated protein kinase (MAPK) and phospholipase C-c signaling pathways, in several types of human cancers, including NSCLC [5]. 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
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