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Updated: Jan 24, 2026
Establishment of a Primary Culture of Patient-derived Soft Tissue Sarcoma
Published on: April 11, 2018
PARP1 expression in soft tissue sarcomas is a poor-prognosis factor and a new potential therapeutic target
François Bertucci1,2,3, Pascal Finetti1, Audrey Monneur2
1Predictive Oncology Laboratory, Marseille Cancer Research Center (CRCM), Institut Paoli-Calmettes, U1068 INSERM, U7258 CNRS, Aix-Marseille University, Marseille, France.
Abstract:
Soft tissue sarcomas (STSs) are aggressive tumors with few efficient systemic therapies. Poly(ADP-ribose) polymerase-1 (PARP1) inhibitors represent an emerging therapeutic option in tumors with genomic instability. The genomics of STSs is complex in more than half of cases, suggesting a high level of inherent DNA damage and genomic instability. Thus, STSs could be efficiently targeted with PARP inhibitors. Promising preclinical results have been reported, but few data are available regarding PARP1 expression in clinical samples. We examined PARP1 mRNA expression in 1464 clinical samples of STS, including 1432 primary tumors and 32 relapses, and searched for correlations with clinicopathological features, including metastasis-free survival (MFS). Expression was heterogeneous across the samples, not different between primary and secondary tumors, and was correlated to PARP1 DNA copy number. In the 1432 primary tumors, the 'PARP1-high' samples were associated with younger patients, more frequent locations at the extremities, superficial trunk and head and neck, more leiomyosarcomas and other STSs and less liposarcomas and myxofibrosarcomas, more grade 3, more high-risk CINSARC tumors, and more 'chromosomically instable' tumors. They were associated with shorter MFS, independently of other significant prognostic features, including the CINSARC signature. We found a strong involvement of genes overexpressed in the 'PARP1-high' samples in cell cycle, DNA replication, and DNA repair. PARP1 expression refines the prediction of MFS in STSs, and similar expression exists in secondary and primary tumors, supporting the development of PARP1 inhibitors.
Insights
High Poly(ADP-ribose) polymerase-1 (PARP1) expression in soft tissue sarcomas (STSs) correlates with aggressive features and poorer metastasis-free survival. This finding supports PARP1 inhibitors as a potential therapy for these aggressive cancers.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Soft tissue sarcomas (STSs) are aggressive cancers with limited systemic treatment options.
- Genomic instability is common in STSs, suggesting potential efficacy of Poly(ADP-ribose) polymerase-1 (PARP1) inhibitors.
- Clinical data on PARP1 expression in STSs are scarce, hindering therapeutic development.
Purpose of the Study:
- To investigate Poly(ADP-ribose) polymerase-1 (PARP1) mRNA expression in a large cohort of soft tissue sarcoma (STS) clinical samples.
- To correlate PARP1 expression with clinicopathological features and metastasis-free survival (MFS) in STSs.
- To evaluate the potential of PARP1 as a therapeutic target and prognostic biomarker in STSs.
Main Methods:
- Quantitative analysis of PARP1 mRNA expression in 1464 soft tissue sarcoma (STS) samples (1432 primary, 32 relapsed).
- Correlation analysis between PARP1 expression levels and clinicopathological variables, including CINSARC signature and metastasis-free survival (MFS).
- Investigation of gene expression patterns associated with high PARP1 expression, focusing on DNA damage and repair pathways.
Main Results:
- PARP1 expression was heterogeneous across STS samples and showed no significant difference between primary and relapsed tumors.
- High PARP1 expression in primary tumors correlated with specific patient demographics, tumor locations, histological subtypes, and higher tumor grade (grade 3).
- PARP1-high tumors were associated with increased chromosomal instability and shorter metastasis-free survival (MFS), independent of other prognostic factors.
- Genes involved in cell cycle, DNA replication, and DNA repair were overexpressed in PARP1-high samples.
Conclusions:
- PARP1 expression is a significant prognostic factor that refines metastasis-free survival (MFS) prediction in soft tissue sarcomas (STSs).
- PARP1 expression levels are similar in primary and relapsed tumors, supporting its potential as a consistent therapeutic target.
- These findings provide a strong rationale for developing Poly(ADP-ribose) polymerase-1 (PARP1) inhibitors for clinical use in soft tissue sarcoma (STS) treatment.
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