Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

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

Authors: Pei-Yu Huang, Ting-Ting Zeng, Xiaojiao Ban, Meng-Qing Li, Bao-Zhu Zhang, Ying-Hui Zhu, Wen-Feng Hua, Hai-Qiang Mai, Li Zhang, Xin-Yuan Guan, Yan Li

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
Ma BB, Hui EP, Chan AT. Systemic approach to improving treatment outcome in nasopharyngeal carcinoma: current and future directions. Cancer Sci. 2008;99(7):1311–8.CrossRefPubMed
2.
Razak AR, Siu LL, Liu FF, Ito E, O’Sullivan B, Chan K. Nasopharyngeal carcinoma: the next challenges. Eur J Cancer. 2010;46(11):1967–78.CrossRefPubMed
3.
4.
Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ, Ma J. How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 2011;80(3):661–8.CrossRefPubMed
5.
Lee AW, Tung SY, Chua DT, Ngan RK, Chappell R, Tung R, Siu L, Ng WT, Sze WK, Au GK, et al. Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2010;102(15):1188–98.CrossRefPubMed
6.
Tjia WM, Sham JS, Hu L, Tai AL, Guan XY. Characterization of 3p, 5p, and 3q in two nasopharyngeal carcinoma cell lines, using region-specific multiplex fluorescence in situ hybridization probes. Cancer Genet Cytogenet. 2005;158(1):61–6.CrossRefPubMed
7.
Lee CH, Fang CY, Sheu JJ, Chang Y, Takada K, Chen JY. Amplicons on chromosome 3 contain oncogenes induced by recurrent exposure to 12-O-tetradecanoylphorbol-13-acetate and sodium n-butyrate and Epstein-Barr virus reactivation in a nasopharyngeal carcinoma cell line. Cancer Genet Cytogenet. 2008;185(1):1–10.CrossRefPubMed
8.
Or YY, Hui AB, Tam KY, Huang DP, Lo KW. Characterization of chromosome 3q and 12q amplicons in nasopharyngeal carcinoma cell lines. Int J Oncol. 2005;26(1):49–56.PubMed
9.
Hui AB, Lo KW, Teo PM, To KF, Huang DP. Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by array based comparative genomic hybridization. Int J Oncol. 2002;20(3):467–73.PubMed
10.
Guan XY, Sham JS, Tang TC, Fang Y, Huo KK, Yang JM. Isolation of a novel candidate oncogene within a frequently amplified region at 3q26 in ovarian cancer. Cancer Res. 2001;61(9):3806–9.PubMed
11.
Clement PM, Henderson CA, Jenkins ZA, Smit-McBride Z, Wolff EC, Hershey JW, Park MH, Johansson HE. Identification and characterization of eukaryotic initiation factor 5A-2. Eur J Biochem. 2003;270(21):4254–63.CrossRefPubMed
12.
Jenkins ZA, Haag PG, Johansson HE. Human eIF5A2 on chromosome 3q25-q27 is a phylogenetically conserved vertebrate variant of eukaryotic translation initiation factor 5A with tissue-specific expression. Genomics. 2001;71(1):101–9.CrossRefPubMed
13.
Guan XY, Fung JM, Ma NF, Lau SH, Tai LS, Xie D, Zhang Y, Hu L, Wu QL, Fang Y, et al. Oncogenic role of eIF-5A2 in the development of ovarian cancer. Cancer Res. 2004;64(12):4197–200.CrossRefPubMed
14.
Tang DJ, Dong SS, Ma NF, Xie D, Chen L, Fu L, Lau SH, Li Y, Li Y, Guan XY. Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma. Hepatology. 2010;51(4):1255–63.CrossRefPubMed
15.
He LR, Zhao HY, Li BK, Liu YH, Liu MZ, Guan XY, Bian XW, Zeng YX, Xie D. Overexpression of eIF5A-2 is an adverse prognostic marker of survival in stage I non-small cell lung cancer patients. Int J Cancer. 2011;129(1):143–50.CrossRefPubMed
16.
Wei JH, Cao JZ, Zhang D, Liao B, Zhong WM, Lu J, Zhao HW, Zhang JX, Tong ZT, Fan S, et al. EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo. Br J Cancer. 2014;110(7):1767–77.CrossRefPubMedPubMedCentral
17.
Zhu W, Cai MY, Tong ZT, Dong SS, Mai SJ, Liao YJ, Bian XW, Lin MC, Kung HF, Zeng YX, et al. Overexpression of EIF5A2 promotes colorectal carcinoma cell aggressiveness by upregulating MTA1 through C-myc to induce epithelial-mesenchymaltransition. Gut. 2012;61(4):562–75.CrossRefPubMed
18.
Lo AK, Liu Y, Wang XH, Huang DP, Yuen PW, Wong YC, Tsao GS. Alterations of biologic properties and gene expression in nasopharyngeal epithelial cells by the Epstein-Barr virus-encoded latent membrane protein 1. Lab Invest. 2003;83(5):697–709.CrossRefPubMed
19.
Wang Y, Wu MC, Sham JS, Zhang W, Wu WQ, Guan XY. Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer. 2002;95(11):2346–52.CrossRefPubMed
20.
Lu TX, Luo W, Zhao C, Wu SX, Chen Y, Cui NJ, Qian JY, Wu JH. A probe of design methods of block shielding facio cervical portals at isocentre for radiotherapy of nasopharyngeal carcinoma. Chin J cancer. 2000;19(10):930–3.
21.
Li Y, Fu L, Li JB, Qin Y, Zeng TT, Zhou J, Zeng ZL, Chen J, Cao TT, Ban X, et al. Increased expression of EIF5A2, via hypoxia or gene amplification, contributes to metastasis and angiogenesis of esophageal squamous cell carcinoma. Gastroenterology. 2014;146(7):1701–13. e1709.CrossRefPubMed
22.
Wong AM, Kong KL, Tsang JW, Kwong DL, Guan XY. Profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs. Cancer. 2012;118(3):698–710.CrossRefPubMed
23.
Yu MC, Ho JH, Ross RK, Henderson BE. Nasopharyngeal carcinoma in Chinese---salted fish or inhaled smoke? Prev Med. 1981;10(1):15–24.CrossRefPubMed
24.
Xu FH, Xiong D, Xu YF, Cao SM, Xue WQ, Qin HD, Liu WS, Cao JY, Zhang Y, Feng QS, et al. An epidemiological and molecular study of the relationship between smoking, risk of nasopharyngeal carcinoma, and Epstein-Barr virus activation. J Natl Cancer Inst. 2012;104(18):1396–410.CrossRefPubMed
25.
Chan AS, To KF, Lo KW, Ding M, Li X, Johnson P, Huang DP. Frequent chromosome 9p losses in histologically normal nasopharyngeal epithelia from southern Chinese. Int J Cancer. 2002;102(3):300–3.CrossRefPubMed
26.
Lo KW, Chung GT, To KF. Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol. 2012;22(2):79–86.CrossRefPubMed
27.
Lo YM, Chan AT, Chan LY, Leung SF, Lam CW, Huang DP, Johnson PJ. Molecular prognostication of nasopharyngeal carcinoma by quantitative analysis of circulating Epstein-Barr virus DNA. Cancer Res. 2000;60(24):6878–81.PubMed
28.
Chua DT, Nicholls JM, Sham JS, Au GK. Prognostic value of epidermal growth factor receptor expression in patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy and radiotherapy. Int J Radiat Oncol Biol Phys. 2004;59(1):11–20.CrossRefPubMed
29.
Huang PY, Li Y, Mai HQ, Luo RZ, Cai YC, Zhang L. Expression of ERCC1 predicts clinical outcome in locoregionally advanced nasopharyngeal carcinoma treated with cisplatin-based induction chemotherapy. Oral Oncol. 2012;48(10):964–8.CrossRefPubMed
30.
Ng WT, Lee MC, Hung WM, Choi CW, Lee KC, Chan OS, Lee AW. Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2011;79(2):420–8.CrossRefPubMed
31.
Lee N, Xia P, Quivey JM, Sultanem K, Poon I, Akazawa C, Akazawa P, Weinberg V, Fu KK. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys. 2002;53(1):12–22.CrossRefPubMed
32.
Liu Y, Du F, Chen W, Yao M, Lv K, Fu P. EIF5A2 is a novel chemoresistance gene in breast cancer. Breast cancer. 2015;22(6):602-07.
33.
Wang FW, Cai MY, Mai SJ, Chen JW, Bai HY, Li Y, Liao YJ, Li CP, Tian XP, Kung HF, et al. Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression. Oncotarget. 2014;5(16):6716–33.CrossRefPubMedPubMedCentral
Metadata
Title
Expression of EIF5A2 associates with poor survival of nasopharyngeal carcinoma patients treated with induction chemotherapy
Authors
Pei-Yu Huang
Ting-Ting Zeng
Xiaojiao Ban
Meng-Qing Li
Bao-Zhu Zhang
Ying-Hui Zhu
Wen-Feng Hua
Hai-Qiang Mai
Li Zhang
Xin-Yuan Guan
Yan Li
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2714-2

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Research article

Galectin-3 interacts with components of the nuclear ribonucleoprotein complex

Research article

Phase II study of TP300 in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma

Research article

High sensitivity isoelectric focusing to establish a signaling biomarker for the diagnosis of human colorectal cancer

Study protocol

Efficacy of night-time compression for breast cancer related lymphedema (LYNC): protocol for a multi-centre, randomized controlled efficacy trial

Study protocol

Development of OXY111A, a novel hypoxia-modifier as a potential antitumor agent in patients with hepato-pancreato-biliary neoplasms - Protocol of a first Ib/IIa clinical trial

Erratum

Erratum to: The anti-tumor effect of the quinoline-3-carboxamide tasquinimod: blockade of recruitment of CD11b+ Ly6Chi cells to tumor tissue reduces tumor growth
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits