Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma.
Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma.
复制标题
着丝粒蛋白F表达在人鼻咽癌中的预后意义和治疗意义
DOI：
10.1186/1476-4598-9-237
复制
发表时间：
2010-09-09
期刊：
影响因子：
37.3
通讯作者：
Zeng MS
中科院分区：
文献类型：
--
作者：
Cao JY;Liu L;Chen SP;Zhang X;Mi YJ;Liu ZG;Li MZ;Zhang H;Qian CN;Shao JY;Fu LW;Xia YF;Zeng MS
背景基因芯片研究表明，与正常鼻咽上皮细胞相比，原代培养的鼻咽癌细胞中着丝粒蛋白F（CENP-F）表达显著上调。本研究的目的是进一步研究CENP-F在鼻咽癌细胞系和组织中的表达水平，以阐明CENP-F在鼻咽癌中表达的临床意义以及CENP-F表达的潜在治疗意义。永生化鼻咽上皮细胞和NPC细胞系。采用实时荧光定量RT-PCR法检测23例鼻咽活检组织中CENP-F mRNA的表达水平，采用免疫组化法检测202例鼻咽癌石蜡切片中CENP-F蛋白的表达水平。应用统计学分析来检验预后相关性。CENP-F潜在的靶向化学品，唑来膦酸（ZOL）和FTI-277单独，或与顺铂，在NPC细胞的细胞毒性测定由MTT assay.ResultsThe水平的CENP-F的mRNA和蛋白质在NPC细胞系高于正常和永生化NPEC。鼻咽癌活检组织中CENP-F mRNA水平较癌旁组织明显升高。免疫组化检测CENP-F在202例鼻咽癌组织中的阳性表达率为48.5%（98/202）。统计学分析显示CENP-F高表达与鼻咽癌T分期（P< 0.001）、临床分期（P< 0.001）、颅底侵犯（P <0.001）、远处转移（P= 0.012）呈正相关，与总生存期呈负相关。多因素分析显示CENP-F表达是患者生存的独立预后指标。此外，我们发现ZOL或FTI-277可以显著增强鼻咽癌细胞系的化疗敏感性（HONE 1和6- 10 B）的CENP-F蛋白高表达对顺铂的抑制作用，而ZOL或FTI-277单独对NPC细胞的抑制作用较小。CENP-F表达与患者的总体存活率相关。此外，我们的数据表明ZOL或FTI-277与顺铂联合治疗NPC的潜在益处，表明CENP-F表达可能具有治疗意义。
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.
登录
查看更多内容
影响因子：
7.5
作者：
Hui, D;Reiman, T;Lai, R
通讯作者：
Lai, R
CENP-F是一种核基质的蛋白质，该核基质在G2晚期聚集在动力学上，并在有丝分裂后迅速降解。
影响因子：
7.8
作者：
LIAO, H;WINKFEIN, RJ;MACK, G;RATTNER, JB;YEN, TJ
通讯作者：
YEN, TJ
影响因子：
2
作者：
Konstantinidou, AE;Korkolopoulou, P;Davaris, P
通讯作者：
Davaris, P
影响因子：
14.5
作者：
Lo, KW;Huang, DP
通讯作者：
Huang, DP
影响因子：
3.8
作者：
Jia WH;Huang QH;Liao J;Ye W;Shugart YY;Liu Q;Chen LZ;Li YH;Lin X;Wen FL;Adami HO;Zeng Y;Zeng YX
通讯作者：
Zeng YX