Uncovering the molecular secrets of Inflammatory Breast Cancer biology: An integrated analysis of three distinct Affymetrix gene expression data sets
A partir de données d'expression de gènes obtenues à l'aide de biopuces Affymetrix sur des patientes atteintes d'un cancer du sein (137 cancers inflammatoires, 252 non inflammatoires), cette étude met notamment en évidence une faible signalisation TGFβ dans les cancers inflammatoires
Purpose: Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here we present the integration of 3 Affymetrix expression data sets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported.
Experimental Design: Affymetrix profiles (HGU133-series) from 137 IBC patients and 252 non-IBC patients (nIBC) were analyzed using unsupervised and supervised techniques. Samples were classified according the molecular subtypes using the PAM50-algorithm. Regression models were used to delineate IBC-specific and molecular subtype-independent changes in gene expression, pathway and transcription factor activation.
Results:Four robust IBC-sample clusters were identified, associated with the different molecular subtypes (P<0.001), all of which were identified in IBC with a similar prevalence as in nIBC, except for the Luminal A subtype (19% vs. 42%; P<0.001) and the HER2-enriched subtype (22% vs. 9%; P<0.001). Supervised analysis identified and validated an IBC-specific, molecular subtype-independent 79-gene signature, which held independent prognostic value in a series of 871 nIBCs. Functional analysis revealed attenuated TGFβ signaling in IBC.
Conclusions:We show that IBC is transcriptionally heterogeneous and that all molecular subtypes described in nIBC are detectable in IBC, albeit with a different frequency. The molecular profile of IBC, bearing molecular traits of aggressive breast tumor biology, shows attenuation of TGFβ signaling, potentially explaining the metastatic potential of IBC tumor cells in an unexpected manner.
Clinical Cancer Research , résumé, 2013