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Updated: Aug 16, 2025
Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays
Published on: February 24, 2023
Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to
Karolina Seborova1,2, Viktor Hlavac1,2, Petr Holy1,2,3
1Toxicogenomics Unit, National Institute of Public Health in Prague, Prague, Czechia.
Abstract:
Epithelial ovarian carcinoma (EOC) is known for high mortality due to diagnosis at advanced stages and frequent therapy resistance. Previous findings suggested that the DNA repair system is involved in the therapeutic response of cancer patients and DNA repair genes are promising targets for novel therapies. This study aimed to address complex inter-relations among gene expression levels, methylation profiles, and somatic mutations in DNA repair genes and EOC prognosis and therapy resistance status. We found significant associations of DUT expression with the presence of peritoneal metastases in EOC patients. The high-grade serous EOC subtype was enriched with TP53 mutations compared to other subtypes. Furthermore, somatic mutations in XPC and PRKDC were significantly associated with worse overall survival of EOC patients, and higher FAAP20 expression in platinum-resistant than platinum-sensitive patients was observed. We found higher methylation of RAD50 in platinum-resistant than in platinum-sensitive patients. Somatic mutations in BRCA1 and RAD9A were significantly associated with higher RBBP8 methylation in platinum-sensitive compared to platinum-resistant EOC patients. In conclusion, we discovered associations of several candidate genes from the DNA repair pathway with the prognosis and platinum resistance status of EOC patients, which deserve further validation as potential predictive biomarkers.
Insights
DNA repair genes impact epithelial ovarian carcinoma (EOC) outcomes. This study links gene expression, mutations, and methylation in DNA repair genes to EOC prognosis and platinum resistance, identifying potential biomarkers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epithelial ovarian carcinoma (EOC) has high mortality, often diagnosed late and resistant to therapy.
- DNA repair pathways are implicated in cancer treatment response, making DNA repair genes potential therapeutic targets.
Purpose of the Study:
- To investigate the relationships between gene expression, methylation, and somatic mutations in DNA repair genes and EOC prognosis and platinum resistance.
- To identify potential predictive biomarkers for EOC treatment outcomes.
Main Methods:
- Analysis of gene expression levels, methylation profiles, and somatic mutations in DNA repair genes.
- Correlation of these molecular features with EOC patient prognosis and platinum sensitivity/resistance status.
Main Results:
- DUT expression associated with peritoneal metastases.
- TP53 mutations frequent in high-grade serous EOC.
- XPC and PRKDC mutations linked to worse survival.
- FAAP20 expression higher in platinum-resistant EOC.
- RAD50 methylation higher in platinum-resistant EOC.
- BRCA1 and RAD9A mutations associated with RBBP8 methylation differences between platinum-sensitive and resistant EOC.
Conclusions:
- Several DNA repair genes show associations with EOC prognosis and platinum resistance.
- These genes represent potential predictive biomarkers for EOC patient outcomes.
- Further validation is needed to confirm their clinical utility.
