CDK activity predicts RCC recurrence

By Shreeya Nanda, Senior medwireNews Reporter

The specific activity of cyclin-dependent kinase (CDK)1 and CDK2 as well as a risk score based on the activity of these enzymes can predict recurrence in patients with renal cell carcinoma (RCC), study findings indicate.

A total of 91 patients with nonmetastatic RCC who had undergone radical nephrectomy between September 1999 and August 2009 were followed up for a median of 37 months. The specific activity of CDK1 and CDK2 was evaluated using the Cell Cycle Profiling system and receiver operating characteristic analysis was used to establish optimal cutoffs for each parameter.

As reported in Urologic Oncology: Seminars and Original Investigations, individuals with a low CDK2 to CDK1 specific activity ratio had significantly improved 5-year recurrence-free survival (RFS) compared with those with a high ratio, at 88.7% versus 54.7%.

The 5-year RFS was 88.7% in patients with malignancies categorised as low risk on the basis of CDK1 and CDK2 activity. This compared with a 5-year RFS of 54.7% in participants with high-risk tumours, a difference that was statistically significant, the researchers report.

Fumiya Hongo (Kyoto Prefectural University of Medicine, Japan) and co-investigators used the Cox proportional hazards model to identify prognostic factors for RFS and found that clinical stage, tumour grade, CDK2 specific activity, CDK2 to CDK1 specific activity ratio and the risk score correlated significantly with RFS.

Multivariate analysis, adjusting for clinical stage and tumour grade, showed that the risk score was an independent and statistically significant prognostic factor in these patients.

Hongo et al explain that molecules involved in cell cycle regulation have been attracting considerable attention as prognostic indicators in cancer, and that previous research has shown that the activity of CDK1 and CDK2 is a significant indictor of relapse in patients with breast cancer.

Highlighting the need for validation in a multicentre study with a larger number of participants, the authors “consider that the CDK-based risk should be a new prognostic factor and a routine laboratory test.”

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