The Clinical Significance of Aurora-A/STK15/BTAK Expression in Human Esophageal Squamous Cell Carcinoma

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Abstract
Purpose: Aurora-A/STK15/BTAK (Aurora-A) 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 Aurora-A in human esophageal squamous cell carcinoma (ESCC). Experimental Design: The expression levels of Aurora-A mRNA were compared in 33 ESCC tissues with that in corresponding normal esophageal epithelium by semiquantitative reverse transcription-PCR, and the distribution patterns and expression levels of Aurora-A protein were immunohistochemically investigated in the ESCC tumors of 142 patients. The results were then separately compared with the clinicopathologic findings of the patients, and the expression of Aurora-A was examined in nine ESCC cell lines and a normal esophageal epithelial cell line using Western blot analysis. Results: The up-regulation of Aurora-A mRNA was found in 30% (10 of 33) of the tumors by semiquantitative reverse transcription-PCR, and protein up-regulation was found in 53% (75 of 142) of the patients by immunohistochemistry. mRNA and protein up-regulation of Aurora-A were correlated with distant lymph node metastasis (P = 0.05 and P = 0.04, respectively), and patients with Aurora-A mRNA or protein up-regulation had a poorer prognosis (P = 0.003 and P = 0.0009, respectively). Furthermore, multivariate analysis revealed that up-regulation of the Aurora-A protein was an independent prognostic factor. In addition, Aurora-A expression in all ESCC cell lines was higher than that in a normal esophageal epithelial cell line. Conclusions: The up-regulation of Aurora-A expression may reflect the malignant behavior of ESCC and may prove useful information as a prognostic factor for ESCC patients.