A Clinically Relevant Gene Signature in Triple-Negative and Basal-Like Breast Cancer

ABSTRACT: Current prognostic gene expression profiles for breast cancer mainly reflect proliferation status and are most useful in ER-positive cancers. Triple-negative breast cancers (TNBCs) are clinically heterogeneous, and prognostic markers and biology-based therapies are needed to better treat this disease. We assembled Affymetrix gene expression data for 579 TNBCs and performed unsupervised analysis to define metagenes that distinguish molecular subsets within TNBC. We used n=394 cases for discovery and n=185 cases for validation. Sixteen metagenes emerged that identified basal-like, apocrine and claudin-low molecular subtypes, or reflected various non-neoplastic cell populations including immune cells, blood, adipocytes, stroma, angiogenesis, and inflammation within the cancer. The expressions of these metagenes were correlated with survival and multivariate analysis was performed including routine clinical and pathological variables. 73% of TNBCs displayed basal-like molecular subtype that correlated with high histological grade and younger age. Survival of basal-like TNBC was not different from non-basal-like TNBC. High expression of immune cell metagenes was associated with good and high expression of inflammation and angiogenesis-related metagenes were associated with poor prognosis. A ratio of high B-cell and low IL-8 metagenes identified 32% of TNBC with good prognosis (HR 0.37, 95% CI 0.22-0.61; P<0.001) and was the only significant predictor in multivariate analysis including routine clincopathological variables. We describe a ratio of high B-cell presence and low IL-8 activity as a powerful new prognostic marker for TNBC. Inhibition of the IL-8 pathway also represents an attractive novel therapeutic target for this disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31519 | GEO | 2011/09/13

SECONDARY ACCESSION(S): PRJNA145507

REPOSITORIES: GEO