Abstract
BackgroundNasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide. Increasing evidence supports that the accumulation of additional genetic and epigenetic abnormalities is important in driving the NPC tumorigenic process. In this study, we aim to investigate the association between EIF5A2 (Eukaryotic translation initiation factor 5A2) expression status and NPC clinical outcomes.MethodsThe expression status of EIF5A2 was investigated in the NPC tissue microarray. Tissues were from 166 NPC patients staging II-IV, collected between 1999 and 2005. All patients were administered 2–3 cycles of DDP (cisplatin) + 5-Fu (5-fluorouracil) induction therapy and then treated with a uniform conventional two-dimensional radiotherapy. Cell motility assay, tumor growth assay and cytotoxicity assay were performed on the EIF5A2 overexpressed cells and control cells. siRNA was also used in the in vitro studies.ResultsPositive staining of EIF5A2 was observed in 85.4 % (105/123) informative tumor cases. Multivariate analyses demonstrated that EIF5A2 was an independent prognostic marker of poor overall survival (OS) (P = 0.041), failure-free survival (FFS) (P = 0.029), and distant failure-free survival (D-FFS) (P = 0.043) in patients with locoregionally advanced NPC patients treated with cisplatin + 5-Fu chemoradiotherapy. The forced expression of EIF5A2 in NPC cells enhanced the cells’ motility and growth ability. Knock-down of EIF5A2 in NPC cells decreased the cell’s motility and growth ability. Our results also demonstrated that EIF5A2 overexpression induced chemoresistance of NPC cells to 5-Fu.ConclusionsOur findings suggested that EIF5A2 expression, as examined by immunohistochemistry, could function as an independent prognostic factor of outcomes in NPC patients with cisplatin + 5-Fu chemoradiotherapy. EIF5A2 might be a novel therapeutic target for the inhibition of NPC progress.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2714-2) contains supplementary material, which is available to authorized users.
Highlights
Nasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide
Our results indicated that Eukaryotic initiation factor 5A2 (EIF5A2) was an independent adverse prognostic marker of overall survival (OS), failure-free survival (FFS), and distant FFS (D-FFS) in NPC patients
Our results demonstrated that EIF5A2 overexpression induced chemoresistance to 5-Fu (5-fluorouracil) in NPC cells
Summary
Nasopharyngeal carcinoma (NPC) is a type of head-neck cancer with a distinguishable geographic and racial distribution worldwide. We aim to investigate the association between EIF5A2 (Eukaryotic translation initiation factor 5A2) expression status and NPC clinical outcomes. The mainstay of treatment for NPC is either radiotherapy or combined chemo-radiotherapy, which demonstrates a cure rate of over 90 % in early-stage patients [3]. Eukaryotic translation initiation factor 5A2 (eIF5A2) is an oncogene at 3q26. It shares 83 % amino acid identity with EIF5A including the critical functional domain necessary for maturation by hypusine modification [10, 11]. 3q26 amplification has been reported in NPC, the expression of eIF5A2, located at 3q26.2, has not been investigated in NPC. Functional study demonstrated that overexpression of EIF5A2 increased cells’ motility and growth ability. Our results demonstrated that EIF5A2 overexpression induced chemoresistance to 5-Fu (5-fluorouracil) in NPC cells
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