Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta-analysis
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Anthony Gonc¸alves Pascal Finetti Renaud Sabatier Marine Gilabert Jose´ Adelaide Jean-Paul Borg Max Chaffanet Patrice Viens Daniel Bir
- چاپ و سال / کشور: 2010
Description
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 metaanalysis 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, andworsemetastasisfree 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.
Breast Cancer Res Treat (2011) 127:273–281 DOI 10.1007/s10549-010-1199-y Received: 4 May 2010 / Accepted: 25 September 2010 / Published online: 11 November 2010
