Specific activity of cyclin-dependent kinase I is a new potential predictor of tumour recurrence in stage II colon cancer

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 recurre...

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Bibliographic Details
Published in:British journal of cancer 2012-01, Vol.106 (1), p.133-140
Main Authors: ZEESTRATEN, Ecm, MAAK, M, ISHIHARA, H, ROSENBERG, R, KUPPEN, P. J. K, JANSSEN, K.-P, SHIBAYAMA, M, SCHUSTER, T, NITSCHE, U, MATSUSHIMA, T, NAKAYAMA, S, GOHDA, K, FRIESS, H, DE VELDE, C. J. H.Van
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Base Sequence
Biological and medical sciences
Biomarkers
Breast cancer
Cancer research
Cancer therapies
Cell cycle
Chemotherapy
Colonic Neoplasms - enzymology
Colonic Neoplasms - pathology
Colorectal cancer
Cyclin-dependent kinases
Cyclin-Dependent Kinases - metabolism
DNA Primers
Female
Fluorescent Antibody Technique
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Kinases
Male
Medical prognosis
Medical research
Medical sciences
Metastasis
Middle Aged
Molecular Diagnostics
Neoplasm Recurrence, Local
Patients
Retrospective Studies
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
Young Adult
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Summary: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. 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. 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. Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2011.504