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Open Access 01-12-2007 | Research article

Pathway analysis of gene signatures predicting metastasis of node-negative primary breast cancer

Authors: Jack X Yu, Anieta M Sieuwerts, Yi Zhang, John WM Martens, Marcel Smid, Jan GM Klijn, Yixin Wang, John A Foekens

Published in: BMC Cancer | Issue 1/2007

Abstract

Background

Published prognostic gene signatures in breast cancer have few genes in common. Here we provide a rationale for this observation by studying the prognostic power and the underlying biological pathways of different gene signatures.

Methods

Gene signatures to predict the development of metastases in estrogen receptor-positive and estrogen receptor-negative tumors were identified using 500 re-sampled training sets and mapping to Gene Ontology Biological Process to identify over-represented pathways. The Global Test program confirmed that gene expression profilings in the common pathways were associated with the metastasis of the patients.

Results

The apoptotic pathway and cell division, or cell growth regulation and G-protein coupled receptor signal transduction, were most significantly associated with the metastatic capability of estrogen receptor-positive or estrogen-negative tumors, respectively. A gene signature derived of the common pathways predicted metastasis in an independent cohort. Mapping of the pathways represented by different published prognostic signatures showed that they share 53% of the identified pathways.

Conclusion

We show that divergent gene sets classifying patients for the same clinical endpoint represent similar biological processes and that pathway-derived signatures can be used to predict prognosis. Furthermore, our study reveals that the underlying biology related to aggressiveness of estrogen receptor subgroups of breast cancer is quite different.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/7/182/prepub

Title: Pathway analysis of gene signatures predicting metastasis of node-negative primary breast cancer
Authors: Jack X Yu
Anieta M Sieuwerts
Yi Zhang
John WM Martens
Marcel Smid
Jan GM Klijn
Yixin Wang
John A Foekens
Publication date: 01-12-2007
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2007
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-7-182

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