Pathway analysis reveals functional convergence of gene expression profiles in breast cancer

Ronglai Shen¹ , Arul M Chinnaiyan² and Debashis Ghosh³

¹Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

²Department of Pathology and Urology, University of Michigan, Ann Arbor, MI, USA

³Departments of Statistics and Public Health Sciences, Penn State University, University Park, PA, USA

author email corresponding author email

BMC Medical Genomics 2008, 1:28doi:10.1186/1755-8794-1-28


Published:	27 June 2008

Abstract

Background

A recent study has shown high concordance of several breast-cancer gene signatures in predicting disease recurrence despite minimal overlap of the gene lists. It raises the question if there are common themes underlying such prediction concordance that are not apparent on the individual gene-level. We therefore studied the similarity of these gene-signatures on the basis of their functional annotations.

Results

We found the signatures did not identify the same set of genes but converged on the activation of a similar set of oncogenic and clinically-relevant pathways. A clear and consistent pattern across the four breast cancer signatures is the activation of the estrogen-signaling pathway. Other common features include BRCA1-regulated pathway, reck pathways, and insulin signaling associated with the ER-positive disease signatures, all providing possible explanations for the prediction concordance.

Conclusion

This work explains why independent breast cancer signatures that appear to perform equally well at predicting patient prognosis show minimal overlap in gene membership.