Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy.
BACKGROUND
Nasopharyngeal 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.


METHODS
The 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.


RESULTS
Positive 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.


CONCLUSIONS
Our 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.
['Huang|Pei-Yu|PY|', 'Zeng|Ting-Ting|TT|', 'Ban|Xiaojiao|X|', 'Li|Meng-Qing|MQ|', 'Zhang|Bao-Zhu|BZ|', 'Zhu|Ying-Hui|YH|', 'Hua|Wen-Feng|WF|', 'Mai|Hai-Qiang|HQ|', 'Zhang|Li|L|', 'Guan|Xin-Yuan|XY|', 'Li|Yan|Y|']
D000328:Adult D000368:Aged D014408:Biomarkers, Tumor D002277:Carcinoma D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D059248:Chemoradiotherapy D002945:Cisplatin D005260:Female D005472:Fluorouracil D006801:Humans D060828:Induction Chemotherapy D008297:Male D008875:Middle Aged D000077274:Nasopharyngeal Carcinoma D009303:Nasopharyngeal Neoplasms D010448:Peptide Initiation Factors D034622:RNA Interference D034741:RNA, Small Interfering D016601:RNA-Binding Proteins D055815:Young Adult
EIF5A2 Nasopharyngeal carcinoma Gene amplification Prognosis