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.
Enhancer of zeste homolog 2 Nuclear expression Renal cell carcinoma Y-Box-binding protein 1
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This work was supported by grants (81202380, 81402094, and 81202100) from the National Natural Science Foundation of China, grants (20111202120016) from Ph.D. Programs Foundation of Ministry of Education of China, grants (12JCQNJC07800, 12JCYBJC15600, and 14JCQNJC11600) from Natural Science Foundation of Tianjin, grant (2013M541189) from China Postdoctoral Science Foundation, and grant (201310062002) Tianjin national undergraduate training programs for innovation and entrepreneurship.
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