Sun Wenze, Song Liping, Ai Ting, Zhang Yingbing, Gao Ying, Cui Jie
Department of Radiation Oncology, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
J Biomed Res. 2013 May;27(3):220-30. doi: 10.7555/JBR.27.20130004. Epub 2013 Apr 25.
The aim of this study was to analyze the correlation of the expression of MET and cyclin D1 and MET gene copy number in non-small cell lung cancer (NSCLC) tissues and patient clinicopathologic characteristics and survival. Sixty-one NSCLC tissue specimens were included in the study. The expression of MET and cyclin D1 was evaluated by immunohistochemistry and MET gene copy number was assessed by quantitative real-time polymerase chain reaction (Q-PCR). Positive expression of MET and cyclin D1 protein and increased MET gene copy number occurred in 59.0%, 59.0% and 18.0% of 61 NSCLC tissues, respectively. MET-positivity correlated with poor differentiation (P = 0.009). Increased MET gene copy number was significantly associated with lymph node metastasis (P = 0.004) and advanced tumor stage (P = 0.048), while the expression of cyclin D1 was not associated with any clinicopathologic parameters. There was a significant correlation between the expression of MET and MET gene copy number (P = 0.002). Additionally, the expression of cyclin D1 had a significant association with the expression of MET as well as MET gene copy number (P = 0.002 and P = 0.017, respectively). MET-positivity and increased MET gene copy number were significantly associated with poor overall survival (P = 0.003 and P < 0.001, respectively) in univariate analysis. Multivariate Cox proportional hazard analysis confirmed that the expression of MET and MET gene copy number were prognostic indicators of NSCLC (P = 0.003 and P = 0.001, respectively). The overexpression of MET and the increased MET gene copy number might be adverse prognostic factors for NSCLC patients. The activation of the MET/cyclin D1 signaling pathway may contribute to carcinogenesis and the development of NSCLC, and may represent a target for therapy.
本研究旨在分析非小细胞肺癌（NSCLC）组织中MET和细胞周期蛋白D1的表达、MET基因拷贝数与患者临床病理特征及生存情况之间的相关性。本研究纳入了61例NSCLC组织标本。采用免疫组织化学法评估MET和细胞周期蛋白D1的表达，采用定量实时聚合酶链反应（Q-PCR）评估MET基因拷贝数。在61例NSCLC组织中，MET和细胞周期蛋白D1蛋白的阳性表达以及MET基因拷贝数增加分别占59.0%、59.0%和18.0%。MET阳性与低分化相关（P = 0.009）。MET基因拷贝数增加与淋巴结转移（P = 0.004）和肿瘤晚期（P = 0.048）显著相关，而细胞周期蛋白D1的表达与任何临床病理参数均无关。MET的表达与MET基因拷贝数之间存在显著相关性（P = 0.002）。此外，细胞周期蛋白D1的表达与MET的表达以及MET基因拷贝数均存在显著相关性（分别为P = 0.002和P = 0.017）。在单因素分析中，MET阳性和MET基因拷贝数增加与总生存期较差显著相关（分别为P = 0.003和P < 0.001）。多因素Cox比例风险分析证实，MET的表达和MET基因拷贝数是NSCLC的预后指标（分别为P = 0.003和P = 0.001）。MET的过表达和MET基因拷贝数增加可能是NSCLC患者的不良预后因素。MET/细胞周期蛋白D1信号通路的激活可能促进NSCLC的发生和发展，并且可能成为治疗靶点。
