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Open Access Research article

A pseudo-R2 measure for selecting genomic markers with crossing hazards functions

Sigrid Rouam12*, Thierry Moreau3 and Philippe Broët124

Author Affiliations

1 Genome Institute of Singapore, Biopolis, Singapore

2 Univ Paris-Sud, U669, Villejuif, F-94807 France

3 Inserm, UMRS 1018, Villejuif, F-94807 France; Univ Paris-Sud, Villejuif, F-94807 France

4 Hôspital Paul Brousse AP-HP, Villejuif, F-94807 France

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BMC Medical Research Methodology 2011, 11:28  doi:10.1186/1471-2288-11-28

Published: 15 March 2011

Abstract

Background

In genomic medical studies, one of the major objectives is to identify genomic factors with a prognostic impact on time-to-event outcomes so as to provide new insights into the disease process. Selection usually relies on statistical univariate indices based on the Cox model. Such model assumes proportional hazards (PH) which is unlikely to hold for each genomic marker.

Methods

In this paper, we introduce a novel pseudo-R2 measure derived from a crossing hazards model and designed for the selection of markers with crossing effects. The proposed index is related to the score statistic and quantifies the extent of a genomic factor to separate patients according to their survival times and marker measurements. We also show the importance of considering genomic markers with crossing effects as they potentially reflect the complex interplay between markers belonging to the same pathway.

Results

Simulations show that our index is not affected by the censoring and the sample size of the study. It also performs better than classical indices under the crossing hazards assumption. The practical use of our index is illustrated in a lung cancer study. The use of the proposed pseudo-R2 allows the identification of cell-cycle dependent genes not identified when relying on the PH assumption.

Conclusions

The proposed index is a novel and promising tool for selecting markers with crossing hazards effects.