Wang Yong, Chen Yajing, Geng Hua, Qi Can, Liu Yunde, Yue Dan
Department of Urology, Tianjin Institute of Urology, Tianjin Medical University Second Hospital, Tianjin, 300211, China.
School of Laboratory Medicine, Tianjin Medical University, Tianjin, 300203, China.
Tumour Biol. 2015 Sep;36(9):7159-66. doi: 10.1007/s13277-015-3417-z. Epub 2015 Apr 17.
Renal cell carcinoma (RCC) is the most common type of kidney cancers in adults, and metastasis represents the major cause of mortality of RCC patients. The Y-box binding protein 1 (YB1) is a multifunctional oncoprotein in various malignancies. Enhancer of zeste homolog 2 (EZH2), a polycomb histone methyltransferase, is a key epigenetic modifier implicated in various cancer metastasis. However, the expression patterns and clinical correlations of both YB1 and EZH2 in RCC remain largely unclear. In this study, the expression of YB1 and EZH2 were examined using immunohistochemistry staining in a study cohort including 165 RCC and 80 tumor adjacent normal tissues. RCC tissues showed a significant higher nuclear expression of YB1 (p < 0.001) and EZH2 (p < 0.001) as compared with the normal counterparts. In addition, YB1 and EZH2 nuclear overexpression were found to be positively associated with RCC stage (p < 0.001 and p = 0.005), Fuhrman tumor grade (p = 0.022 and p = 0.044), and metastasis (p < 0.001 and p = 0.009). Overall survival analysis indicated patients with YB1 (p = 0.004, HR 5.656 (2.006-10.944)) and/or EZH2 (p = 0.006, HR 4.551 (2.124-9.438)) nuclear overexpression correlated with poor survival. More interestingly, YB1 and EZH2 nuclear expression was correlated (p = 0.005). Further studies demonstrated that EZH2 expression was significantly downregulated in YB1 knockdown RCC cell lines. Functionally, YB1 knockdown inhibited RCC invasion in vitro. In conclusion, YB1 and EZH2 expression was correlated and associated with RCC incidence, tumor stage, grade, metastasis, and survival.
肾细胞癌（RCC）是成人中最常见的肾癌类型，转移是RCC患者死亡的主要原因。Y盒结合蛋白1（YB1）是多种恶性肿瘤中的一种多功能癌蛋白。zeste同源物2增强子（EZH2）是一种多梳组蛋白甲基转移酶，是参与各种癌症转移的关键表观遗传修饰因子。然而，YB1和EZH2在RCC中的表达模式及临床相关性仍不清楚。在本研究中，通过免疫组织化学染色检测了165例RCC组织和80例肿瘤旁正常组织中YB1和EZH2的表达。与正常组织相比，RCC组织中YB1（p＜0.001）和EZH2（p＜0.001）的核表达显著更高。此外，发现YB1和EZH2核过表达与RCC分期（p＜0.001和p = 0.005）、Fuhrman肿瘤分级（p = 0.022和p = 0.044）及转移（p＜0.001和p = 0.009）呈正相关。总生存分析表明，YB1（p = 0.004，HR 5.656（2.006 - 10.944））和/或EZH2（p = 0.006，HR 4.551（2.124 - 9.438））核过表达的患者生存较差。更有趣的是，YB1和EZH2的核表达相关（p = 0.005）。进一步研究表明，在YB1敲低的RCC细胞系中EZH2表达显著下调。在功能上，YB1敲低抑制了RCC的体外侵袭。总之，YB1和EZH2的表达相关，并与RCC的发生、肿瘤分期、分级、转移及生存有关。
