Dataset Information

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

ABSTRACT:

Background

Our 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.

Methods

Real-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.

Results

The 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.

Conclusion

Our 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.

SUBMITTER: Cao JY

PROVIDER: S-EPMC2944187 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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

Cao Jing-Yan JY Liu Li L Chen Shu-Peng SP Zhang Xing X Mi Yan-Jun YJ Liu Zhi-Gang ZG Li Man-Zhi MZ Zhang Hua H Qian Chao-Nan CN Shao Jian-Yong JY Fu Li-Wu LW Xia Yun-Fei YF Zeng Mu-Sheng MS

Molecular cancer 20100909

<h4>Background</h4>Our 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.<h4>Methods</ ...[more]

PMID: 20828406

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Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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