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Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer

The Pharmacogenomics Journal volume 11, pages 93–99 (2011)Cite this article

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Abstract

Aurora kinases are conserved eukaryotic serine–threonine kinases, which serve as key regulators of mammalian mitosis. Several studies revealed a distinct correlation between inaccurate chromosome segregation, leading to chromosomal number instability, cancer progression and poor outcome. The aim of this study was to investigate the correlation of Aurora kinases A (AURKA) and B (AURKB) with overall survival (OS) by quantifying gene expression analysis and evaluation of single-nucleotide polymorphisms (SNPs) in human colorectal cancer samples and assessing the associations with clinicopathological features. We evaluated intratumoral gene expression levels and SNPs of AURKA and -B from 41 patients with metastatic colorectal cancer (mCRC). Patients with a high expression level of AURKB (>1.28) lived significantly shorter (n=11, median OS=6.4 months, 95% confidence interval (CI): 3.0–14.5 months) compared with patients with a low expression level (⩽1.28) (n=30, median OS=18.4 months, 95% CI: 14.7–27.8 months, P=0.026, Wald's test). Patients harboring any G-allele in AURKB 885A>G showed a significantly decreased OS (P=0.05, log-rank test). We did not find any associations with clinicopathological variables and AURKA gene expression levels. Our results suggest a potential role for AURKB inhibition in patients with mCRC; thereby supporting its potential role as a target in mCRC.

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Acknowledgements

This work was funded by the NIH grant 5 P30CA14089-27I and the Dhont Family Foundation and performed in the Sharon A. Carpenter Laboratory at USC/Norris CCC.

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  1. A Pohl and M Azuma: Both authors contributed equally to this work.

Authors and Affiliations

  1. Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    A Pohl, W Zhang, Y Ning, T Winder & H-J Lenz

  2. Response Genetics, Inc, Los Angeles, CA, USA

    M Azuma & K Danenberg

  3. Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    D Yang & H-J Lenz

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  1. A Pohl
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Correspondence to H-J Lenz.

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Pohl, A., Azuma, M., Zhang, W. et al. Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer. Pharmacogenomics J 11, 93–99 (2011). https://doi.org/10.1038/tpj.2010.18

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