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

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. The Pharmacogenomics Journal (2011) 11, 93-99; doi:10.1038/tpj.2010.18; published online 6 April 2010