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


METHODS
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.
Reiter
Rudolf
R
Department of Otolaryngology Head and Neck Surgery, Universitätsklinikum Ulm, Ulm, Germany.
Gais
Peter
P
Jütting
Uta
U
Steuer-Vogt
Miriam K
MK
Pickhard
Anja
A
Bink
Karin
K
Rauser
Sandra
S
Lassmann
Silke
S
Höfler
Heinz
H
Werner
Martin
M
Walch
Axel
A
D064096:Aurora Kinase A; D064127:Aurora Kinases; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics*; D018385:Centrosome / Q000473:pathology; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013329:Structure-Activity Relationship; D015996:Survival Rate; D046888:Tissue Array Analysis / Q000379:methods; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases