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Updated: Nov 6, 2025
Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays
Published on: February 24, 2023
Associations between DNA Damage and PD-L1 Expression in Ovarian Cancer, a Potential Biomarker for Clinical Response
Elise K Mann1,2, Kevin J Lee1,2, Dongquan Chen3
1Department of Physiology and Cell Biology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA.
Abstract:
Programmed death ligand-1 (PD-L1) inhibitors are currently under investigation as a potential treatment option for ovarian cancer. Although this therapy has shown promise, its efficacy is highly variable among patients. Evidence suggests that genomic instability influences the expression of PD-L1, but little is known about this relationship in ovarian cancer. To examine the relationship between PD-L1 expression and genomic instability, we measured DNA damage using Repair Assisted Damage Detection (RADD). We then correlated the presence of persistent DNA damage in the ovarian tumor with protein expression of PD-L1 using immunohistochemistry. Ovarian tumors showed a high prevalence of oxidative DNA damage. As the level of oxidative DNA damage increased, we saw a significant correlation with PD-L1 expression. The highest correlation between DNA damage and PD-L1 expression was observed for mucinous ovarian tumors (r = 0.82), but a strong correlation was also observed for high grade serous and endometrioid tumors (r = 0.67 and 0.69, respectively). These findings link genomic instability to PD-L1 protein expression in ovarian cancer and suggest that persistent DNA damage can be used as a potential biomarker for patient selection for immunotherapy treatment.
Insights
Genomic instability, measured by DNA damage, correlates with Programmed death ligand-1 (PD-L1) expression in ovarian tumors. This suggests DNA damage may predict immunotherapy response in ovarian cancer patients.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Programmed death ligand-1 (PD-L1) inhibitors are being explored for ovarian cancer treatment, but patient responses vary.
- Genomic instability's role in PD-L1 expression in ovarian cancer is not well understood.
Purpose of the Study:
- To investigate the relationship between genomic instability and PD-L1 protein expression in ovarian tumors.
- To determine if DNA damage can serve as a biomarker for immunotherapy selection in ovarian cancer.
Main Methods:
- DNA damage was quantified using Repair Assisted Damage Detection (RADD).
- PD-L1 protein expression was assessed via immunohistochemistry.
- Correlation analysis was performed between DNA damage levels and PD-L1 expression.
Main Results:
- Ovarian tumors frequently exhibited oxidative DNA damage.
- A significant positive correlation was found between increasing levels of oxidative DNA damage and PD-L1 expression.
- Strong correlations were observed across various ovarian tumor subtypes, including mucinous, high-grade serous, and endometrioid.
Conclusions:
- Genomic instability, indicated by persistent DNA damage, is linked to PD-L1 protein expression in ovarian cancer.
- Persistent DNA damage may serve as a predictive biomarker for selecting ovarian cancer patients eligible for PD-L1 targeted immunotherapy.
