| Objective: c-MET is an oncogene expressed in various epithelial tissues and multiple tumors. It is closely associated with proliferation, metastasis, angiogenesis and drug-resistance of tumors and often overexpressed or amplified. However, the relationship between c-MET and non-small-cell lung carcinoma remains unclear and is being argued heatedly. In order to clarify this relationship, we summarized previous researches in this field and conducted this meta-analysis. This study aims to discuss the prognositic values and clinicopathological features of c-MET in patients with non-small-cell lung carcinoma. Both the level of protein expression and gene copy number are included. Overall survival and disease-free survival are chosen as criteria to evaluate the prognostic role of c-MET.Methods: Pubmed, Embase, Science Direct, Cochrane Library, CNKI, Wanfang databases were searched to collect relevant articles. All researches about prognositic effects and clinicopathological features of c-MET in patients with non-small-cell lung carcinoma were screened. Included articles were analyzed using STATA12.0 software and pooled hazard ratio(HR) and oddz ratio(OR) were selected to assess the effects of c-MET protein expression and gene copy number on the prognostic importance and clinicopathological significance, respectively. Begg’s test and Egger’s test were applied to estimate the publication bias.Results: 49 articles were included in this research. 37 of them are in English while 12 of them are in Chinese. Meta-analysis of survival analysis: in the aspect of protein, compared with non-small-cell lung carcinoma patients with c-MET negative or low expression, patients with c-MET positive or high expression had worse overall survival(univariate HR=1.41, 95%CI : 1.01-1.99; multivariate HR=2.19, 95%CI :1.42-3.39) and decreased disease-free survival(univariate HR=2.54, 95%CI:1.43-4.50; multivariate HR=2.19, 95%CI:1.11-4.34). In terms of gene copy number, univariate analysis showed that compared with non-small-cell lung carcinoma patients with normal or decreased gene copy number of c-MET, patients with amplified gene copy number of c-MET tended to have worse overall survival(HR=1.46, 95%CI:1.11-1.93). However, multivariate analysis indicated there was no definite association between amplified c-MET gene copy number and overall survival(HR=1.34, 95%CI:0.98-1.83). Moreover, evidences to date could not relate amplification of c-MET gene with disease-free survival in patients with non-small-cell lung carcinoma directly(univariate HR=1.54, 95%CI : 0.92-2.56; multivariate HR=1.17, 95%CI :0.77-1.79). Results of clinicopathological characteristics: positive or high expression of c-MET protein was closely related to histology(adenocarcinoma VS. others; OR=0.48, 95%CI: 0.32-0.72), histology(squamous cell carcinoma VS. others; OR=1.99, 95%CI: 1.35-2.93), T stage(large tumor VS. small tumor; OR=1.57, 95%CI: 1.18-2.08), lymph node metastasis(yes VS. no; OR=2.03, 95%CI: 1.35-3.04), TNM stage(stage 3-4 VS. stage 1-2; OR=1.76, 95%CI: 1.29-2.41), blood vessel invasion(yes VS. no; OR=1.79, 95%CI: 1.07-2.99), lymphatic vessel invasion(yes VS. no; OR=1.96, 95%CI: 1.13-3.37) and pleural invasion(yes VS. no; OR=3.47, 95%CI: 1.93-6.27). Increased gene copy number of c-MET was closely associated with smoking(yes VS. no; OR=1.65, 95%CI: 1.29-2.10), histology(squamous cell carcinoma VS. others; OR=0.74, 95%CI: 0.60-0.92), differentiation(poorly VS. well; OR=1.48, 95%CI: 1.06-2.07), T stage(large tumor VS. small tumor; OR=1.75, 95%CI: 1.17-2.62), TNM stage(stage 3-4 VS. stage 1-2; OR=1.73, 95%CI: 1.38-2.16), lymphatic vessel invasion(yes VS. no; OR=2.20, 95%CI: 1.26-3.84) and pleural invasion(yes VS. no; OR=2.92, 95%CI: 1.46-5.83).Conclusions: Both univariate and multivariate analyses revealed expression of c-MET protein could be used to evaluate overall survival and recurrence or progression of patients with non-small-cell lung carcinoma. Only univariate analysis displayed c-MET gene copy number could role as indicator of overall survival while multivariate analysis could not define the function of amplified c-MET gene copy number in overall survival. Furthmore, neither univariate nor multivariate anlysis could prove there was a connection between c-MET gene copy number and recurrence or progression of non-small-cell lung carcinoma. For patients with non-small-cell lung carcinoma, high expression of c-MET protein was more common in patients with adenocarcinoma, large tumor, positive lymph node metastasis, TNM stage 3-4,blood vessel invasion, lymphatic vessel invasion and pleural invasion. Increased c-MET gene copy number was more prevalent in patients with smoking history, poorly differentiated tumor cells, large tumor, TNM stage 3-4, lymphatic vessel invasion and pleural invasion.Moreover, high expression of c-MET protein as well as amplified c-MET gene was less seen in patients with squamous cell carcinoma. |
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