An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-08

AUTHORS

Andrew E Teschendorff, Ahmad Miremadi, Sarah E Pinder, Ian O Ellis, Carlos Caldas

ABSTRACT

BACKGROUND: Estrogen receptor (ER)-negative breast cancer specimens are predominantly of high grade, have frequent p53 mutations, and are broadly divided into HER2-positive and basal subtypes. Although ER-negative disease has overall worse prognosis than does ER-positive breast cancer, not all ER-negative breast cancer patients have poor clinical outcome. Reliable identification of ER-negative tumors that have a good prognosis is not yet possible. RESULTS: We apply a recently proposed feature selection method in an integrative analysis of three major microarray expression datasets to identify molecular subclasses and prognostic markers in ER-negative breast cancer. We find a subclass of basal tumors, characterized by over-expression of immune response genes, which has a better prognosis than the rest of ER-negative breast cancers. Moreover, we show that, in contrast to ER-positive tumours, the majority of prognostic markers in ER-negative breast cancer are over-expressed in the good prognosis group and are associated with activation of complement and immune response pathways. Specifically, we identify an immune response related seven-gene module and show that downregulation of this module confers greater risk for distant metastasis (hazard ratio 2.02, 95% confidence interval 1.2-3.4; P = 0.009), independent of lymph node status and lymphocytic infiltration. Furthermore, we validate the immune response module using two additional independent datasets. CONCLUSION: We show that ER-negative basal breast cancer is a heterogeneous disease with at least four main subtypes. Furthermore, we show that the heterogeneity in clinical outcome of ER-negative breast cancer is related to the variability in expression levels of complement and immune response pathway genes, independent of lymphocytic infiltration. More... »

PAGES

r157

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/gb-2007-8-8-r157

DOI

http://dx.doi.org/10.1186/gb-2007-8-8-r157

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052735338

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17683518


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