-- mRNA expression in human breast cancer: a meta-analysis
Résumé
Although poly(ADP-ribose) polymerase-1 (PARP1) inhibition is a recent promising therapy in breast cancer, PARP1 expression in this disease is not known. Using DNA microarray and array-based comparative genomic hybridization (arrayCGH), we examined mRNA expression and copy number alterations in 326 invasive breast cancer samples and normal breast (NB) samples. A meta-analysis was performed on a large public retrospective gene expression data set ( = 2,485) to analyze correlation between mRNA expression and molecular subtypes and clinico-pathological parameters. was overexpressed in 58% of cancers, and its expression was heterogeneous between tumors. ArrayCGH data revealed an association between mRNA overexpression and gain/amplification at the locus ( < 1.0E-8). Meta-analysis showed that expression was higher in basal breast cancers ( < 1.0E-72), but overexpression was also found in other subtypes. expression correlated with high grade, medullary histological type, tumor size, and worse metastasis-free survival (MFS; HR = 1.12 [1.04-1.22], = 0.004) and overall survival (OS; HR = 1.16 [1.04-1.29], = 0.006). In multivariate analysis, expression had an independent prognostic value for MFS, which was restricted to patients untreated with any adjuvant chemotherapy. These data demonstrate overexpression of in a large number of breast cancers and support the development of PARP inhibitors in basal subtype, but also potentially in other breast cancer subtypes.
Domaines
Sciences du Vivant [q-bio]
Origine : Fichiers produits par l'(les) auteur(s)
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