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.

3rd Faculty of Medicine Charles University Prague Czechia

Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czechia

Department of Cancer Genetics Institute for Cancer Research Oslo University Hospital The Norwegian Radium Hospital Oslo Norway

Department of Gynecology and Obstetrics 3rd Faculty of Medicine and University Hospital Kralovske Vinohrady Prague Czechia

Department of Gynecology and Obstetrics University Hospital in Pilsen Charles University Pilsen Czechia

Department of Medical Genetics Institute of Clinical Medicine Faculty of Medicine University of Oslo Oslo Norway

Department of Oncology and Radiotherapeutics Faculty of Medicine in Pilsen and University Hospital Charles University Pilsen Czechia

Department of Pathology and Molecular Medicine Motol University Hospital 2nd Faculty of Medicine Charles University Prague Czechia

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czechia

Institute of Experimental Medicine Czech Academy of Sciences Prague Czechia

Laboratory of Cancer Treatment and Tissue Regeneration Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czechia

Toxicogenomics Unit National Institute of Public Health Prague Prague Czechia

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