Abstract
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.
Highlights
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
centromeric proteins (CENPs)-F expression is upregulated in NPC cell lines To investigate the expression levels of CENP-F, realtime RT-PCR, and western blotting analysis were conducted on the samples of normal nasopharyngeal epithelial cells (NPEC2), the immortalized nasopharyngeal epithelial cells (NPEC2 Bmi-1), and various NPC cell lines
Consistent with mRNA levels, high expression of CENP-F protein was observed in all of the NPC cell lines, whereas there was no detectable expression of CENP-F in NPEC2 and NPEC2 Bmi-1 (Fig. 1B)
Summary
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. Nasopharyngeal carcinoma (NPC) is a disease with remarkable geographic and racial distributions worldwide. It is one of the most common cancers in Southeastern Asia and is highly prevalent among populations originating from Southern China where the yearly incidence rate of NPC is 25-50 per 100,000 people [1,2]. Nasopharyngeal carcinogenesis is a multistep process with morphological progression involving multiple genetic and epigenetic events [6]. Identification of molecular and biological changes that occur during carcinogenesis and progression could facilitate investigation of the pathology of the disease and generate new prognostic markers to more accurately predict patients’ clinical outcome, helping to individualize treatments for NPC patients
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