title: Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer.
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.
authors.affiliation: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pohl
authors.forename: M
authors.initials: M
authors.lastname: Azuma
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Ning
authors.forename: T
authors.initials: T
authors.lastname: Winder
authors.forename: K
authors.initials: K
authors.lastname: Danenberg
authors.forename: H-J
authors.initials: HJ
authors.lastname: Lenz
mesh_terms: D000328:Adult; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases