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Dotan E , Meropol NJ , Zhu F , Zambito F , Bove B , Cai KQ , Godwin AK , Golemis EA , Astsaturov I , Cohen SJ
Relationship of increased aurora kinase A gene copy number, prognosis and response to chemotherapy in patients with metastatic colorectal cancer
British Journal of Cancer. 2012 Feb;106(4) :748-755
PMID: WOS:000300303200020    PMCID: PMC3322945   
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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.
Dotan, E. Meropol, N. J. Zhu, F. Zambito, F. Bove, B. Cai, K. Q. Godwin, A. K. Golemis, E. A. Astsaturov, I. Cohen, S. J. AMGEN[3840610]; Comprehensive Cancer Center at Fox Chase[3P30CA006927-47S4]; NIH[R01CA63366] This study was supported by AMGEN Medical Oncology Fellowship Award (Grant number: 3840610) and by the core grant of the Comprehensive Cancer Center Program at Fox Chase - 3P30CA006927-47S4. Dr Golemis is supported by NIH funding (Grant number: R01CA63366). 35 Nature publishing group London 892rl