Overexpression of YB1 and EZH2 are associated with cancer metastasis and poor prognosis in renal cell carcinomas.

Abstract

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.

• Authors: Yong Wang, Yajing Chen, Hua Geng, Can Qi, Yunde Liu, Dan Yue
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 9 Pg. 7159-66 (Sep 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25877750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Y-Box-Binding Protein 1
• YBX1 protein, human
• EZH2 protein, human
• Enhancer of Zeste Homolog 2 Protein
• Polycomb Repressive Complex 2

Topics

• Adult
• Aged
• Biomarkers, Tumor (biosynthesis, genetics)
• Carcinoma, Renal Cell (genetics, pathology)
• Cell Proliferation (genetics)
• Disease-Free Survival
• Enhancer of Zeste Homolog 2 Protein
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lymphatic Metastasis
• Male
• Middle Aged
• Polycomb Repressive Complex 2 (biosynthesis, genetics)
• Prognosis
• Y-Box-Binding Protein 1 (biosynthesis, genetics)