Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta-analysis.
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 PARP1 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 (n = 2,485) to analyze correlation between PARP1 mRNA expression and molecular subtypes and clinico-pathological parameters. PARP1 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 PARP1 locus (P < 1.0E-8). Meta-analysis showed that PARP1 expression was higher in basal breast cancers (P < 1.0E-72), but overexpression was also found in other subtypes. PARP1 expression correlated with high grade, medullary histological type, tumor size, and worse metastasis-free survival (MFS; HR = 1.12 [1.04-1.22], P = 0.004) and overall survival (OS; HR = 1.16 [1.04-1.29], P = 0.006). In multivariate analysis, PARP1 expression had an independent prognostic value for MFS, which was restricted to patients untreated with any adjuvant chemotherapy. These data demonstrate overexpression of PARP1 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.
Département d'Oncologie Médicale and U891 INSERM, Centre de Recherche en Cancérologie de Marseille, Institut Paoli-Calmettes, 232 Bd. Ste-Marguerite, 13009 Marseille, France. goncalvesa@marseille.fnclcc.fr
Anthony
A
Gonçalves
Pascal
P
Finetti
Renaud
R
Sabatier
Marine
M
Gilabert
José
J
Adelaide
Jean-Paul
JP
Borg
Max
M
Chaffanet
Patrice
P
Viens
Daniel
D
Birnbaum
François
F
Bertucci
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D016019:Survival Analysis
D012333:RNA, Messenger; D011065:Poly(ADP-ribose) Polymerases