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Bioinformatics Advance Access published online on March 21, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl110
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© The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received July 11, 2005
Revised March 20, 2006
Accepted March 20, 2006

Article

Identifying gene expression changes in breast cancer that distinguish early and late relapse among uncured patients

Philippe Broët 1 *, Vladimir A. Kuznetsov 2, Jonas Bergh 3, Edison Liu 2, and Lance D. Miller 2

1 Faculté de Médecine - Université Paris-XI, IFR69, 16 Avenue Paul Vaillant Couturier 94807 Villejuif Cedex, France
2 Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore
3 Department of Oncology and Pathology, Radiumhemmet, Karolinska Institute and Hospital, S-171 76 Stockholm, Sweden

* To whom correspondence should be addressed.
Philippe Broët, E-mail: broet{at}vjf.inserm.fr


  Abstract

Motivation: In recent years, microarray technology has revealed many tumor-expressed genes prognostic of clinical outcomes in early-stage breast cancer patients. However, in the presence of cured patients, evaluating gene effect on time to relapse is quite complex since it may affect either the probability of never experiencing a relapse (cure effect) or the time to relapse among the uncured patients (disease progression effect) or both. In this context, we propose a simple and efficient method for identifying gene expression changes that characterize early and late recurrence for uncured patients.

Results: Simulation results show the good performance of the proposed statistic for detecting a disease progression effect. In a study of early-stage breast cancer, our results show that the proposed statistic provides a more powerful basis for gene selection than the classical Cox model-based statistic. From a biological perspective, many of the genes identified here as associated with the speed of disease recurrence have known roles in tumorigenesis.

Associate Editor: John Quackenbush
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