Article (Scientific journals)
Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers.
Boukerroucha, Meriem; Josse, Claire; El Guendi, Sonia et al.
2015In BMC Cancer, 15 (1), p. 755
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Keywords :
BRCA1; TNBC; Breast Cancer; miRNA
Abstract :
[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.
Disciplines :
Oncology
Biochemistry, biophysics & molecular biology
Genetics & genetic processes
Author, co-author :
Boukerroucha, Meriem ;  Université de Liège - ULiège > Doct. sc. bioméd. & pharma. (Bologne)
Josse, Claire  ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
El Guendi, Sonia ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Boujemla, Bouchra ;  ULg-GIGA > Génétique Humaine
Freres, Pierre;  CHU Liège - GIGA > Oncologie Médicale
Marée, Raphaël  ;  Université de Liège > GIGA-Research
Wenric, Stéphane ;  Université de Liège > Département des sciences cliniques > Oncologie
SEGERS, Karin ;  Centre Hospitalier Universitaire de Liège - CHU > Génétique
COLLIGNON, Joëlle  ;  Centre Hospitalier Universitaire de Liège - CHU > Service d'oncologie médicale
Jerusalem, Guy  ;  CHU Liège > Oncologie Médicale
Bours, Vincent ;  Université de Liège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Language :
English
Title :
Evaluation of BRCA1-related molecular features and microRNAs as prognostic factors for triple negative breast cancers.
Publication date :
2015
Journal title :
BMC Cancer
eISSN :
1471-2407
Publisher :
BioMed Central, London, United Kingdom
Volume :
15
Issue :
1
Pages :
755
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 03 December 2015

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