Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma

Molecular Cancer

Research

Jian-Yong Shao¹  Xing Zhang²  Shu-Peng Chen³  Hua Zhang³  Man-Zhi Li³  Yan-Jun Mi³  Mu-Sheng Zeng³  Li-Wu Fu³  Jing-Yan Cao⁴  Chao-Nan Qian⁵  Li Liu⁶  Yun-Fei Xia⁶  Zhi-Gang Liu⁶ 

[1] State Key Laboratory of Oncology in South China, China;State Key Laboratory of Oncology in South China, China;Department of Biotherapy, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, China;Department of Experimental Research, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, China;Department of Experimental Research, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China;Department of Medical Oncology, The 3rd Affiliated Hospital of Harbin Medical University, 150040, Harbin, China;State Key Laboratory of Oncology in South China, China;Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China;State Key Laboratory of Oncology in South China, China;Department of Radiotherapy, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China;

关键词: Zoledronic Acid;    CNE1 Cell;    Nasopharyngeal Epithelial Cell;    HONE1 Cell;    Final Staining Score;   

DOI  :  10.1186/1476-4598-9-237

 received in 2010-04-21, accepted in 2010-09-09,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundOur recent cDNA microarray data showed that centromere protein F (CENP-F) is significantly upregulated in primary cultured nasopharyngeal carcinoma (NPC) tumor cells compared with normal nasopharyngeal epithelial cells. The goal of this study was to further investigate the levels of CENP-F expression in NPC cell lines and tissues to clarify the clinical significance of CENP-F expression in NPC as well as the potential therapeutic implications of CENP-F expression.MethodsReal-time RT-PCR and western blotting were used to examine CENP-F expression levels in normal primary nasopharyngeal epithelial cells (NPEC), immortalized nasopharyngeal epithelial cells and NPC cell lines. Levels of CENP-F mRNA were determined by real-time RT-PCR in 23 freshly frozen nasopharyngeal biopsy tissues, and CENP-F protein levels were detected by immunohistochemistry in paraffin sections of 202 archival NPC tissues. Statistical analyses were applied to test for prognostic associations. The cytotoxicities of CENP-F potential target chemicals, zoledronic acid (ZOL) and FTI-277 alone, or in combination with cisplatin, in NPC cells were determined by the MTT assay.ResultsThe levels of CENP-F mRNA and protein were higher in NPC cell lines than in normal and immortalized NPECs. CENP-F mRNA level was upregulated in nasopharyngeal carcinoma biopsy tissues compared with noncancerous tissues. By immunohistochemical analysis, CENP-F was highly expressed in 98 (48.5%) of 202 NPC tissues. Statistical analysis showed that high expression of CENP-F was positively correlated with T classification (P < 0.001), clinical stage (P < 0.001), skull-base invasion (P < 0.001) and distant metastasis (P = 0.012) inversely correlated with the overall survival time in NPC patients. Multivariate analysis showed that CENP-F expression was an independent prognostic indicator for the survival of the patient. Moreover, we found that ZOL or FTI-277 could significantly enhance the chemotherapeutic sensitivity of NPC cell lines (HONE1 and 6-10B) with high CENP-F expression to cisplatin, although ZOL or FTI-277 alone only exhibited a minor inhibitory effect to NPC cells.ConclusionOur data suggest that CENP-F protein is a valuable marker of NPC progression, and CENP-F expression is associated with poor overall survival of patients. In addition, our data indicate a potential benefit of combining ZOL or FTI-277 with cisplatin in NPC suggesting that CENP-F expression may have therapeutic implications.

【 授权许可】

Unknown   
© Cao et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.