title: miRNA expression profiling of inflammatory breast cancer identifies a 5-miRNA signature predictive of breast tumor aggressiveness.
abstract: IBC (inflammatory breast cancer) is a rare but very aggressive form of breast cancer with a particular phenotype. The molecular mechanisms responsible for IBC remain largely unknown. In particular, genetic and epigenetic alterations specific to IBC remain to be identified. MicroRNAs, a class of small noncoding RNAs able to regulate gene expression, are deregulated in breast cancer and may therefore serve as tools for diagnosis and prediction. This study was designed to determine miRNA expression profiling (microRNAome) in IBC. Quantitative RT-PCR was used to determine expression levels of 804 miRNAs in a screening series of 12 IBC compared to 31 non-stage-matched non-IBC and 8 normal breast samples. The differentially expressed miRNAs were then validated in a series of 65 IBC and 95 non-IBC. From a set of 18 miRNAs of interest selected from the screening series, 13 were differentially expressed with statistical significance in the validation series of IBC compared to non-IBC. Among these, a 5-miRNA signature comprising miR-421, miR-486, miR-503, miR-720 and miR-1303 was shown to be predictive for IBC phenotype with an overall accuracy of 89%. Moreover, multivariate analysis showed that this signature was an independent predictor of poor Metastasis-Free Survival in non-IBC patients.
authors.affiliation: Laboratoire d'oncogénétique, Institut Curie, Hopital Rene Huguenin, 35 rue Dailly, Saint-Cloud, France. florence.lerebours@curie.net
authors.forename: Florence
authors.initials: F
authors.lastname: Lerebours
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cizeron-Clairac
authors.forename: Aurelie
authors.initials: A
authors.lastname: Susini
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Mouret-Fourme
authors.forename: Catherine
authors.initials: C
authors.lastname: Belichard
authors.forename: Etienne
authors.initials: E
authors.lastname: Brain
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Alberini
authors.forename: Frédérique
authors.initials: F
authors.lastname: Spyratos
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D058922:Inflammatory Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D013534:Survival
chemical_list: D014408:Biomarkers, Tumor; C547665:MIRN421 microRNA, human; C560945:MIRN486 microRNA, human; C545473:MIRN503 microRNA, human; C568636:MIRN720 microRNA, human; D035683:MicroRNAs
keywords: breast cancer prognosis; inflammatory breast cancer; miRNA profiles; miRNA signature