Published online before print June 13, 2008

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Journal of Molecular Diagnostics 2008, Vol. 10, No. 4
Copyright © 2008 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2008.080011

Development of a Clinically Feasible Molecular Assay to Predict Recurrence of Stage II Colon Cancer

Yuqiu Jiang^*, Graham Casey, Ian C. Lavery, Yi Zhang^*, Dmitri Talantov^*, Michelle Martin-McGreevy, Marek Skacel, Elena Manilich, Abhijit Mazumder^*, David Atkins^*, Conor P. Delaney and Yixin Wang^*

From Veridex, LLC, a Johnson & Johnson Company, * San Diego, California; the Department of Colorectal Surgery and the Department of Cancer Biology, Cleveland Clinic Foundation, Cleveland, Ohio; and the Division of Colorectal Surgery, University Hospitals of Cleveland, Cleveland, Ohio

The 5-year survival rate for patients with Stage II colon cancer is approximately 75%. However, there is no clinical test available to identify the 25% of patients at high risk of recurrence. We have previously identified a 23-gene signature that predicts individual risk for recurrence. The present study tested this gene signature in an independent group of 123 Stage II patients, and the 23-gene signature was highly informative in identifying patients with distant recurrence in both univariate (hazard ratio [HR] 2.51) and multivariate analyses (HR, 2.40). The composition of this representative patient group also allowed us to refine the 23-gene signature to a 7-gene signature that exhibited a similar prognostic power in both univariate (HR, 2.77) and multivariate analyses (HR, 2.87). Furthermore, we developed this prognostic signature into a clinically feasible test with real-time quantitative PCR using standard fixed paraffin-embedded tumor tissues. When a 110-patient cohort was evaluated with the PCR assay, the 7-gene signature, demonstrated to be a strong prognostic factor in both univariate (HR, 6.89) and multivariate analyses (HR, 14.2). These results clearly show the prognostic value of the predefined gene signature for Stage II colon cancer patients. The ability to identify colon cancer patients with an unfavorable outcome may help patients at high risk for recurrence to seek more aggressive therapy.