Reference : Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors fo...
Scientific journals : Article
Human health sciences : Oncology
Life sciences : Genetics & genetic processes
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/188844
Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers.
English
Boukerroucha, Meriem mailto [Université de Liège - ULg > > > Doct. sc. bioméd. & pharma. (Bologne)]
Josse, Claire mailto [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine >]
El Guendi, Sonia mailto [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine >]
Boujemla, Bouchra mailto [ULg-GIGA > > Génétique Humaine > >]
Freres, Pierre mailto [CHU Liège - GIGA > > Oncologie Médicale > >]
Marée, Raphaël mailto [Université de Liège > > GIGA-Research >]
Wenric, Stéphane mailto [Université de Liège > Département des sciences cliniques > Oncologie >]
SEGERS, Karin mailto [Centre Hospitalier Universitaire de Liège - CHU > > Génétique >]
COLLIGNON, Joëlle mailto [Centre Hospitalier Universitaire de Liège - CHU > > Service d'oncologie médicale >]
Jerusalem, Guy mailto [CHU Liège > > Oncologie Médicale > >]
Bours, Vincent mailto [Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine > > >]
2015
BMC cancer
15
1
755
Yes (verified by ORBi)
International
1471-2407
1471-2407
England
[en] BRCA1 ; TNBC ; Breast Cancer ; miRNA
[en] BACKGROUND: The BRCA1 gene plays a key role in triple negative breast cancers (TNBCs), in which its expression can be lost by multiple mechanisms: germinal mutation followed by deletion of the second allele; negative regulation by promoter methylation; or miRNA-mediated silencing. This study aimed to establish a correlation among the BRCA1-related molecular parameters, tumor characteristics and clinical follow-up of patients to find new prognostic factors. METHODS: BRCA1 protein and mRNA expression was quantified in situ in the TNBCs of 69 patients. BRCA1 promoter methylation status was checked, as well as cytokeratin 5/6 expression. Maintenance of expressed BRCA1 protein interaction with BARD1 was quantified, as a marker of BRCA1 functionality, and the tumor expression profiles of 27 microRNAs were determined. RESULTS: miR-548c-5p was emphasized as a new independent prognostic factor in TNBC. A combination of the tumoral expression of miR-548c and three other known prognostic parameters (tumor size, lymph node invasion and CK 5/6 expression status) allowed for relapse prediction by logistic regression with an area under the curve (AUC) = 0.96. BRCA1 mRNA and protein in situ expression, as well as the amount of BRCA1 ligated to BARD1 in the tumor, lacked any associations with patient outcomes, likely due to high intratumoral heterogeneity, and thus could not be used for clinical purposes. CONCLUSIONS: In situ BRCA1-related expression parameters could be used for clinical purposes at the time of diagnosis. In contrast, miR-548c-5p showed a promising potential as a prognostic factor in TNBC.
http://hdl.handle.net/2268/188844
10.1186/s12885-015-1740-9
http://www.biomedcentral.com/1471-2407/15/755

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