Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer.
Pharmacogenomics J
; 11(2): 93-9, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-20368716
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Proteínas Serina-Treonina Quinasas
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos