Abstract
Purpose
The purpose of this work was to investigate the relationship between Aurora-B, FOXM1, and clinical outcomes in patients with nasopharyngeal carcinoma (NPC) who were treated with a combination of induction chemotherapy and radiotherapy.
Patients and methods
The expression of Aurora-B and FOXM1 were investigated by immunohistochemistry using a tissue microarray (TMA) containing samples from 166 NPC patients who were treated with cisplatin (DDP) + fluorouracil (5-FU) induction chemotherapy and radiotherapy between 1999 and 2005. The relationship of Aurora-B, FOXM1, and survival of these NPC patients was analyzed.
Results
Informative TMA results were obtained in 91 tumor cases for Aurora-B and 93 tumor cases for FOXM1. The 8-year failure-free survival rate (FFS) for the Aurora-B-negative and Aurora-B-positive group was 65.6 and 37.3 %, respectively (p = 0.024), and the 8-year distant FFS (D-FFS) rate was 65.6 and 41.5 %, respectively (p = 0.047). The 8-year overall survival (OS) in the FOXM1-negative group was moderately higher than in the FOXM1-positive group (58.4 vs 39.1 %, p = 0.081). Cox regression analysis revealed that for FFS, Aurora-B expression was a significant prognostic factor (p = 0.025), while for D-FFS, Aurora-B expression was a marginally significant prognostic factor (p = 0.056). When FOXM1 expression was analyzed, the Cox regression analyses showed that FOXM1 expression was a marginally significant prognostic factor (p = 0.056) for OS. Correlation analysis showed that Aurora-B and FOXM1 expression had no significant correlation.
Conclusion
Aurora-B and FOXM1 were both adverse prognostic markers for NPC patients treated with chemoradiotherapy. However, the two markers had no significant correlation.
Zusammenfassung
Ziel
Ziel war die Untersuchung der Beziehung zwischen Aurora-B, FOXM1 und den klinischen Ergebnissen bei Patienten mit nasopharyngealem Karzinom (NPC), die mit einer Kombinationstherapie aus Induktionschemotherapie und Radiotherapie behandelt wurden.
Patienten und Methoden
Die Expression von Aurora-B und FOXM1 wurde durch Immunohistochemie mittels Gewebemikroarray (TMA) mit Proben von 166 Patienten mit NPC durchgeführt, die zwischen 1999 und 2005 mit Cisplatin (DDP) + Fluorouracil-(5-FU-)Induktionschemotherapie und Radiotherapie behandelt worden waren. Die Beziehung von Aurora-B, FOXM1 und dem Überleben dieser Patienten mit NPC wurde analysiert.
Ergebnisse
Informative TMA-Ergebnisse zu Aurora-B wurden bei 91 Tumorpatienten und zu FOXM1 bei 93 Tumorpatienten erzielt. Die 8-Jahres-Überlebensrate ohne Therapieversagen (FFS, “failure-free survival”,) betrug in der Aurora-B-negativen Gruppe 65,6% und in der Aurora-B-positiven Gruppe 37,3% (p = 0,024). Die fernmetastasenfreie 8-Jahres-FFS-(D-FFS-)Rate betrug jeweils 65,6 bzw. 41,5% (p = 0,047). Das 8-Jahres-Gesamtüberleben (OS, “overall survival”) in der FOXM1-negativen Gruppe war mittelgradig höher als in der FOXM1-positiven Gruppe (58,4 vs. 39,1%; p = 0,081). Die Cox-Regressionsanalyse zeigte, dass die Aurora-B-Expression für das FFS ein signifikanter prognostischer Faktor war (p = 0,025); für das D-FFS war die Aurora-B-Expression ein geringfügig signifikanter prognostischer Faktor (p = 0,056). Bei der Analyse der FOXM1-Expression zeigten die Cox-Regressionsanalysen, dass die FOXM1-Expression ein geringfügig signifikanter prognostischer Faktor für OS war (p = 0,056). Die Korrelationsanalyse zeigte, dass die Aurora-B- und FOXM1-Expression nicht signifikant korreliert waren.
Schlussfolgerung
Aurora-B und FOXM1 waren beide ungünstige prognostische Marker für Patienten mit NPC, die mit Chemoradiotherapie behandelt wurden. Dennoch zeigten die beiden Marker keine signifikante Korrelation.
Similar content being viewed by others
Reference
Razak AR, Siu LL, Liu FF et al (2010) Nasopharyngeal carcinoma: the next challenges. Eur J Cancer 46:1967–1978
Yeh SA, Tang Y, Lui CC et al (2005) Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone. Int J Radiat Oncol Biol Phys 62:672–679
Lee AW, Sze WM, Au JS et al (2005) Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys 61:1107–1116
Le QT, Tate D, Koong A et al (2003) Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 56:1046–1054
Lee N, Xia P, Quivey JM et al (2002) Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys 53:12–22
Baujat B, Audry H, Bourhis J et al (2006) Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys 64:47–56
Langendijk JA, Leemans CR, Buter J et al (2004) The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol 22:4604–4612
Mehra R, Serebriiskii IG, Burtness B et al (2013) Aurora kinases in head and neck cancer. Lancet Oncol 14:e425–e435
Carmena M, Earnshaw WC (2003) The cellular geography of aurora kinases. Nat Rev Mol Cell Biol 4:842–854
Bonet C, Giuliano S, Ohanna M et al (2012) Aurora B is regulated by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway and is a valuable potential target in melanoma cells. J Biol Chem 287:29887–29898
Erpolat OP, Gocun PU, Akmansu M et al (2012) High expression of nuclear survivin and Aurora B predicts poor overall survival in patients with head and neck squamous cell cancer. Strahlenther Onkol 188:248–254
Tovuu LO, Utsunomiya T, Imura S et al (2014) The role of Aurora B expression in non-tumor liver tissues of patients with hepatocellular carcinoma. Int J Clin Oncol 19:622–628
Takeshita M, Koga T, Takayama K et al (2013) Aurora-B overexpression is correlated with aneuploidy and poor prognosis in non-small cell lung cancer. Lung Cancer 80:85–90
Wang Y, Wu MC, Sham JS et al (2002) Prognostic significance of c-myc and AIB1 amplification in hepatocellular carcinoma. A broad survey using high-throughput tissue microarray. Cancer 95:2346–2352
Liu ZG, Yi W, Tao YL et al (2012) Aurora-A is an efficient marker for predicting poor prognosis in human nasopharyngeal carcinoma with aggressive local invasion: 208 cases with a 10-year follow-up from a single institution. Oncol Lett 3:1237–1244
Qi G, Ogawa I, Kudo Y et al (2007) Aurora-B expression and its correlation with cell proliferation and metastasis in oral cancer. Virchows Arch 450:297–302
Vischioni B, Oudejans JJ, Vos W et al (2006) Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients. Mol Cancer Ther 5:2905–2913
Yasen M, Mizushima H, Mogushi K et al (2009) Expression of Aurora B and alternative variant forms in hepatocellular carcinoma and adjacent tissue. Cancer Sci 100:472–480
Chen YJ, Chen CM, Twu NF et al (2009) Overexpression of Aurora B is associated with poor prognosis in epithelial ovarian cancer patients. Virchows Arch 455:431–440
Dees EC, Cohen RB, von Mehren M et al (2012) Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Clin Cancer Res 18:4775–4784
Bonner JA, Harari PM, Giralt J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578
Yang J, Ikezoe T, Nishioka C et al (2007) AZD1152, a novel and selective aurora B kinase inhibitor, induces growth arrest, apoptosis, and sensitization for tubulin depolymerizing agent or topoisomerase II inhibitor in human acute leukemia cells in vitro and in vivo. Blood 110:2034–2040
Mortlock AA, Foote KM, Heron NM et al (2007) Discovery, synthesis, and in vivo activity of a new class of pyrazoloquinazolines as selective inhibitors of aurora B kinase. J Med Chem 50:2213–2224
Jiang L, Wang P, Chen H (2014) Overexpression of FOXM1 is associated with metastases of nasopharyngeal carcinoma. Ups J Med Sci 119:324–332
Chen H, Yang C, Yu L et al (2012) Adenovirus-mediated RNA interference targeting FOXM1 transcription factor suppresses cell proliferation and tumor growth of nasopharyngeal carcinoma. J Gene Med 14:231–240
Acknowledgments
This work was supported by National High Technology Research and Development Program of China (863 Program No. 2012AA02A501 and 2012AA02A206); Clinical Research of Special Funds of Wu Jieping Medical Foundation (No. 320.6750.14270).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
P.-Y. Huang, Y. Li, D.-H. Luo, X. Hou, T.-T. Zeng, M.-Q. Li, H.-Q. Mai, and L. Zhang state that there are no conflicts of interest.
All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies
Additional information
Pei-Yu Huang and Yan Li contributed equally to this article.
Rights and permissions
About this article
Cite this article
Huang, PY., Li, Y., Luo, DH. et al. Expression of Aurora-B and FOXM1 predict poor survival in patients with nasopharyngeal carcinoma. Strahlenther Onkol 191, 649–655 (2015). https://doi.org/10.1007/s00066-015-0840-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00066-015-0840-4