Zhong Hongbin, Chen Bin, Neves Henrique, Xing Jinchun, Ye Youxin, Lin Ying, Zhuang Guohong, Zhang Shu-Dong, Huang Jiyi, Kwok Hang Fai
Xiang'an Branch, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People's Republic of China.
Faculty of Health Sciences, University of Macau, Taipa, Macau SAR.
Cancer Manag Res. 2017 Nov 15;9:637-647. doi: 10.2147/CMAR.S146528. eCollection 2017.
Minichromosome maintenance (MCM) proteins play an essential role in DNA replication. They have been shown to be overexpressed in various types of cancer. However, the role of this family in renal cell carcinoma (RCC) is widely unknown. In this study, we have identified a number of RCC datasets in the Gene Expression Omnibus database and also investigated the correlation between the expression levels of MCM genes and clinicopathological parameters. We found that the expression levels of MCM genes are positively correlated with one another. Expression levels of MCM2, MCM5, MCM6, and MCM7, but not of MCM3 and MCM4, were higher in RCC compared to paired adjacent normal tissue. Only the expression level of MCM4, but not of other MCMs, was positively correlated with tumor grade. In addition, a high-level expression of MCM2 in either primary tumor or metastases of RCC predicted a shorter disease-free survival time, while a high-level expression of MCM4 or MCM6 in primary tumor was also associated with poorer disease-free survival. Interestingly, we also demonstrated that patients with their primary RCC overexpressing 2 or more MCM genes had a shorter disease-free survival time, while those with RCC metastases overexpressing 3 or more MCM genes had a shorter disease-free survival. Importantly, we also demonstrated that overexpression of MCM genes is an independent predictor for survival in RCC patients. Our results suggest that MCM2-7 genes may be an important prognostic marker for patients with RCC.
微小染色体维持(MCM)蛋白在DNA复制中起着至关重要的作用。它们已被证明在各种类型的癌症中过度表达。然而,这个家族在肾细胞癌(RCC)中的作用却鲜为人知。在本研究中,我们在基因表达综合数据库中识别了多个RCC数据集,并研究了MCM基因表达水平与临床病理参数之间的相关性。我们发现MCM基因的表达水平彼此呈正相关。与配对的相邻正常组织相比,RCC中MCM2、MCM5、MCM6和MCM7的表达水平较高,而MCM3和MCM4的表达水平则不然。只有MCM4的表达水平与肿瘤分级呈正相关,而其他MCMs则不然。此外,RCC原发肿瘤或转移灶中MCM2的高表达预示着无病生存期较短,而原发肿瘤中MCM4或MCM6的高表达也与较差的无病生存期相关。有趣的是,我们还证明,原发性RCC中过表达2个或更多MCM基因的患者无病生存期较短,而RCC转移灶中过表达3个或更多MCM基因的患者无病生存期较短。重要的是,我们还证明MCM基因的过表达是RCC患者生存的独立预测因素。我们的结果表明,MCM2 - 7基因可能是RCC患者的一个重要预后标志物。