title: Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer.
abstract: BACKGROUND
  There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer.
  
  
  METHODS
  In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples.
  
  
  RESULTS
  Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA ≥11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours.
  
  
  CONCLUSIONS
  Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.
authors: Department of Surgery, Leiden University Medical Center, 2300 Leiden, The Netherlands.
authors: E C M
authors: EC
authors: Zeestraten
authors: M
authors: M
authors: Maak
authors: M
authors: M
authors: Shibayama
authors: T
authors: T
authors: Schuster
authors: U
authors: U
authors: Nitsche
authors: T
authors: T
authors: Matsushima
authors: S
authors: S
authors: Nakayama
authors: K
authors: K
authors: Gohda
authors: H
authors: H
authors: Friess
authors: C J H
authors: CJ
authors: van de Velde
authors: H
authors: H
authors: Ishihara
authors: R
authors: R
authors: Rosenberg
authors: P J K
authors: PJ
authors: Kuppen
authors: K-P
authors: KP
authors: Janssen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D017931:DNA Primers; D018844:Cyclin-Dependent Kinases