a clinically relevant gene signature in triple negative and basal-like breast cancer临床相关的基因签名三阴乳腺癌和官腔.pdfVIP

Rody et al. Breast Cancer Research 2011, 13:R97 /content/13/5/R97 RESEARCH ARTICLE Open Access A clinically relevant gene signature in triple negative and basal-like breast cancer 1† 1*† 2 3 1 1 Achim Rody , Thomas Karn , Cornelia Liedtke , Lajos Pusztai , Eugen Ruckhaeberle , Lars Hanker , 1 1 1 4 5 6 1 Regine Gaetje , Christine Solbach , Andre Ahr , Dirk Metzler , Marcus Schmidt , Volkmar Müller , Uwe Holtrich and Manfred Kaufmann1 Abstract Introduction: Current prognostic gene expression profiles for breast cancer mainly reflect proliferation status and are most useful in ER-positive cancers. Triple negative breast cancers (TNBC) are clinically heterogeneous and prognostic markers and biology-based therapies are needed to better treat this disease. Methods: We assembled Affymetrix gene expression data for 579 TNBC 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. Results: Seventy-three percent of TNBC displayed basal-like molecular subtype that correlated with high histological grade and younger age. Survival of basal-like TNBC was not diffe