TY - JOUR
T1 - Specific activity of cyclin-dependent kinase i is a new potential predictor of tumour recurrence in stage II colon cancer
AU - Zeestraten, E. C.M.
AU - Maak, M.
AU - Shibayama, M.
AU - Schuster, T.
AU - Nitsche, U.
AU - Matsushima, T.
AU - Nakayama, S.
AU - Gohda, K.
AU - Friess, H.
AU - Van De Velde, C. J.H.
AU - Ishihara, H.
AU - Rosenberg, R.
AU - Kuppen, P. J.K.
AU - Janssen, K. P.
PY - 2012/1/3
Y1 - 2012/1/3
N2 - 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. Conclusion: Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.
AB - 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. Conclusion: Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.
KW - biomarker
KW - colorectal cancer
KW - cyclin-dependent kinase
KW - metastasis
KW - prognosis
UR - http://www.scopus.com/inward/record.url?scp=84855339541&partnerID=8YFLogxK
U2 - 10.1038/bjc.2011.504
DO - 10.1038/bjc.2011.504
M3 - Article
C2 - 22108518
AN - SCOPUS:84855339541
SN - 0007-0920
VL - 106
SP - 133
EP - 140
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 1
ER -
