Relationship of increased aurora kinase A gene copy number, prognosis and response to chemotherapy in patients with metastatic colorectal cancer.
Br J Cancer
; 106(4): 748-55, 2012 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-22240781
ABSTRACT
BACKGROUND:
Increased Aurora kinase A gene copy number (AURKA-CN) has been reported in metastatic colorectal cancer (mCRC), with unknown relationship to clinical outcome. We correlated increased AURKA-CN in mCRC tumours with KRAS mutation status, overall and progression-free survival (OS, PFS).METHODS:
Sixty-one mCRC tumours were analysed for AURKA-CN using q-PCR, and KRAS mutation status by direct sequencing. Expression of AURKA protein was analysed by immunohistochemistry. Cox-proportional hazard method, Kaplan-Meier curves and log-rank statistics were used to estimate and compare the hazard ratios and median survival between the groups.RESULTS:
In all, 68% of tumour exhibited high AURKA-CN, and 29% had a KRAS mutation, without correlation between the two. Patients with high AURKA-CN tumours had longer median OS (48.6 vs 18.8 months, P=0.01), with stronger trend among KRAS wild-type tumours (median OS not reached vs 18.8 months, P=0.003). Progression-free survival was longer on first-line or second-line chemotherapy among patients with KRAS wild-type and high vs low AURKA-CN (first 17.6 vs 5.13 months, P=0.04; second 10.4 vs 5.1 months, P=0.01). AURKA-CN level did not affect outcomes among patients with KRAS mutant tumours.CONCLUSION:
Increased AURKA-CN is common in mCRC tumours and is associated with longer OS and longer PFS during chemotherapy, particularly in KRAS wild-type tumours.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Proteínas Proto-Oncogênicas
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Proteínas Serina-Treonina Quinases
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Proteínas ras
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Dosagem de Genes
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos