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MET、细胞周期蛋白D1及MET基因拷贝数在非小细胞肺癌中的预后价值

Prognostic value of MET, cyclin D1 and MET gene copy number in non-small cell lung cancer.

作者信息

Sun Wenze, Song Liping, Ai Ting, Zhang Yingbing, Gao Ying, Cui Jie

机构信息

Department of Radiation Oncology, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.

出版信息

J Biomed Res. 2013 May;27(3):220-30. doi: 10.7555/JBR.27.20130004. Epub 2013 Apr 25.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa74/3664729/595ffd032cde/jbr-27-03-220-g001.jpg

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