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Published on: May 17, 2019
Poly(ADP-ribose) polymerase-1 mRNA expression in human breast cancer: a meta-analysis
Anthony Gonçalves1, Pascal Finetti, Renaud Sabatier
1Département 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
Abstract:
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.
Insights
Poly(ADP-ribose) polymerase-1 (PARP1) is overexpressed in most breast cancers, particularly basal subtypes. High PARP1 expression correlates with aggressive features and poorer survival, supporting PARP inhibitor development.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Poly(ADP-ribose) polymerase-1 (PARP1) inhibition shows promise for breast cancer treatment.
- PARP1 expression levels in breast cancer are not well understood.
- Understanding PARP1 expression is crucial for evaluating PARP inhibitor efficacy.
Purpose of the Study:
- To investigate PARP1 mRNA expression and copy number alterations in invasive breast cancer.
- To analyze the correlation between PARP1 expression and molecular subtypes, clinico-pathological parameters, and patient survival.
- To assess the potential of PARP1 as a therapeutic target in breast cancer subtypes.
Main Methods:
- DNA microarray and array-based comparative genomic hybridization (arrayCGH) were used on 326 invasive breast cancer samples.
- A meta-analysis of a large public gene expression dataset (n = 2,485) was performed.
- Correlation analyses were conducted for PARP1 expression with molecular subtypes, clinico-pathological parameters, and survival outcomes (metastasis-free survival [MFS] and overall survival [OS]).
Main Results:
- PARP1 was overexpressed in 58% of breast cancers, with heterogeneous expression patterns.
- Overexpression was significantly associated with gain/amplification at the PARP1 locus (P < 1.0E-8).
- PARP1 expression was highest in basal breast cancers (P < 1.0E-72) but also elevated in other subtypes.
- PARP1 expression correlated with high grade, medullary type, larger tumor size, and worse MFS (HR = 1.12) and OS (HR = 1.16).
- PARP1 expression demonstrated independent prognostic value for MFS in patients not receiving adjuvant chemotherapy.
Conclusions:
- PARP1 is overexpressed in a significant proportion of breast cancers.
- These findings support the development of PARP inhibitors for basal breast cancer subtypes.
- PARP1 inhibition may also be beneficial for other breast cancer subtypes, warranting further investigation.
