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

被引:0
作者
A Pohl
M Azuma
W Zhang
D Yang
Y Ning
T Winder
K Danenberg
H-J Lenz
机构
[1] Sharon A. Carpenter Laboratory,Division of Medical Oncology
[2] Norris Comprehensive Cancer Center,Department of Preventive Medicine
[3] Keck School of Medicine,undefined
[4] University of Southern California,undefined
[5] Response Genetics,undefined
[6] Inc,undefined
[7] Norris Comprehensive Cancer Center,undefined
[8] Keck School of Medicine,undefined
[9] University of Southern California,undefined
来源
The Pharmacogenomics Journal | 2011年 / 11卷
关键词
metastatic colorectal cancer; Aurora kinase B; overall survival; molecular markers;
D O I
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中图分类号
学科分类号
摘要
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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页码:93 / 99
页数:6
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