Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma

被引:166
作者
Reiter, Rudolf
Gais, Peter
Juetting, Uta
Steuer-Vogt, Miriam K.
Pickhard, Anja
Bink, Karin
Rauser, Sandra
Lassmann, Silke
Hoefler, Heinz
Werner, Martin
Walch, Axel
机构
[1] GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Pathol, D-85764 Neuherberg, Germany
[2] GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Biomath & Biometry, D-85764 Neuherberg, Germany
[3] Univ Ulm Klinikum, Dept Otolaryngol Head & Neck Surg, Ulm, Germany
[4] Tech Univ Munich, Dept Otolaryngol Head & Neck Surg, D-8000 Munich, Germany
[5] Univ Freiburg Klinikum, Inst Pathol, Freiburg, Germany
关键词
D O I
10.1158/1078-0432.CCR-05-1650
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Aurora kinase A (AURKA/STK15/BTAK) encodes a serine/threonine kinase associated with chromosomal distribution and its up-regulation induces chromosomal instability, thereby leading to aneuploidy and cell transformation in several types of cancer. In this study, we investigated the role of AURKA in head and neck squamous cell carcinoma (HNSCC). Experimental Design: The mRNA expression levels of AURKA were compared in tumor tissues of 66 HNSCC patients with those in corresponding normal squamous epithelium by real-time quantitative reverse transcriptase-PCR. In addition, the association between AURKA mRNA and protein expression, centrosome abnormalities, and aneuploidy was studied in a subset of cases (n = 34). All molecular variables were correlated to histomorphologic findings and clinical follow-up data of the patients. Results: AURKA mRNA up-regulation was significantly associated with tumor stage and the occurrence of regional lymph node, as well as distant metastasis (P < 0.0001 for all). Similarly, a correlation was found for protein expression and the occurrence of regional lymph node (P = 0.0183) and distant metastasis (P = 0.03). The mRNA was positively associated with protein expression (P = 0.003) and centrosome abnormalities (P = 0.03). Cox regression analysis revealed that AURKA mRNA up-regulation. correlated with disease-free survival of the patients (P = 0.03) as well as shorter overall survival (P < 0,001). Conclusions: We conclude that the up-regulation of AURKA mRNA may play a critical role in the tumor progression of HNSCC and provides useful information as a prognostic factor for HNSCC patients.
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页码:5136 / 5141
页数:6
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