title: Relationship of increased aurora kinase A gene copy number, prognosis and response to chemotherapy in patients with metastatic colorectal cancer.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA. efrat.dotan@fccc.edu
authors.forename: E
authors.initials: E
authors.lastname: Dotan
authors.forename: N J
authors.initials: NJ
authors.lastname: Meropol
authors.forename: F
authors.initials: F
authors.lastname: Zhu
authors.forename: F
authors.initials: F
authors.lastname: Zambito
authors.forename: B
authors.initials: B
authors.lastname: Bove
authors.forename: K Q
authors.initials: KQ
authors.lastname: Cai
authors.forename: A K
authors.initials: AK
authors.lastname: Godwin
authors.forename: E A
authors.initials: EA
authors.lastname: Golemis
authors.forename: I
authors.initials: I
authors.lastname: Astsaturov
authors.forename: S J
authors.initials: SJ
authors.lastname: Cohen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D064096:Aurora Kinase A; D064127:Aurora Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins