Format

Send to

Choose Destination
PLoS One. 2013 Dec 11;8(12):e82125. doi: 10.1371/journal.pone.0082125. eCollection 2013.

A prognostic gene signature for metastasis-free survival of triple negative breast cancer patients.

Author information

1
Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois, United States of America.
2
Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
3
Departments of Statistics, Ecology and Evolution, Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois, United States of America.

Abstract

Although triple negative breast cancers (TNBC) are the most aggressive subtype of breast cancer, they currently lack targeted therapies. Because this classification still includes a heterogeneous collection of tumors, new tools to classify TNBCs are urgently required in order to improve our prognostic capability for high risk patients and predict response to therapy. We previously defined a gene expression signature, RKIP Pathway Metastasis Signature (RPMS), based upon a metastasis-suppressive signaling pathway initiated by Raf Kinase Inhibitory Protein (RKIP). We have now generated a new BACH1 Pathway Metastasis gene signature (BPMS) that utilizes targets of the metastasis regulator BACH1. Specifically, we substituted experimentally validated target genes to generate a new BACH1 metagene, developed an approach to optimize patient tumor stratification, and reduced the number of signature genes to 30. The BPMS significantly and selectively stratified metastasis-free survival in basal-like and, in particular, TNBC patients. In addition, the BPMS further stratified patients identified as having a good or poor prognosis by other signatures including the Mammaprint® and Oncotype® clinical tests. The BPMS is thus complementary to existing signatures and is a prognostic tool for high risk ER-HER2- patients. We also demonstrate the potential clinical applicability of the BPMS as a single sample predictor. Together, these results reveal the potential of this pathway-based BPMS gene signature to identify high risk TNBC patients that can respond effectively to targeted therapy, and highlight BPMS genes as novel drug targets for therapeutic development.

PMID:
24349199
PMCID:
PMC3859562
DOI:
10.1371/journal.pone.0082125
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center