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

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...

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Autores principales: Cao, Jing-Yan, Liu, Li, Chen, Shu-Peng, Zhang, Xing, Mi, Yan-Jun, Liu, Zhi-Gang, Li, Man-Zhi, Zhang, Hua, Qian, Chao-Nan, Shao, Jian-Yong, Fu, Li-Wu, Xia, Yun-Fei, Zeng, Mu-Sheng
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944187/
https://www.ncbi.nlm.nih.gov/pubmed/20828406
http://dx.doi.org/10.1186/1476-4598-9-237
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author Cao, Jing-Yan
Liu, Li
Chen, Shu-Peng
Zhang, Xing
Mi, Yan-Jun
Liu, Zhi-Gang
Li, Man-Zhi
Zhang, Hua
Qian, Chao-Nan
Shao, Jian-Yong
Fu, Li-Wu
Xia, Yun-Fei
Zeng, Mu-Sheng
author_facet Cao, Jing-Yan
Liu, Li
Chen, Shu-Peng
Zhang, Xing
Mi, Yan-Jun
Liu, Zhi-Gang
Li, Man-Zhi
Zhang, Hua
Qian, Chao-Nan
Shao, Jian-Yong
Fu, Li-Wu
Xia, Yun-Fei
Zeng, Mu-Sheng
author_sort Cao, Jing-Yan
collection PubMed
description 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.
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spelling pubmed-29441872010-09-24 Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma Cao, Jing-Yan Liu, Li Chen, Shu-Peng Zhang, Xing Mi, Yan-Jun Liu, Zhi-Gang Li, Man-Zhi Zhang, Hua Qian, Chao-Nan Shao, Jian-Yong Fu, Li-Wu Xia, Yun-Fei Zeng, Mu-Sheng Mol Cancer Research 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. BioMed Central 2010-09-09 /pmc/articles/PMC2944187/ /pubmed/20828406 http://dx.doi.org/10.1186/1476-4598-9-237 Text en Copyright ©2010 Cao et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 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.
spellingShingle Research
Cao, Jing-Yan
Liu, Li
Chen, Shu-Peng
Zhang, Xing
Mi, Yan-Jun
Liu, Zhi-Gang
Li, Man-Zhi
Zhang, Hua
Qian, Chao-Nan
Shao, Jian-Yong
Fu, Li-Wu
Xia, Yun-Fei
Zeng, Mu-Sheng
Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma
title Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma
title_full Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma
title_fullStr Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma
title_full_unstemmed Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma
title_short Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma
title_sort prognostic significance and therapeutic implications of centromere protein f expression in human nasopharyngeal carcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944187/
https://www.ncbi.nlm.nih.gov/pubmed/20828406
http://dx.doi.org/10.1186/1476-4598-9-237
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