AUTHOR=Seborova Karolina , Hlavac Viktor , Holy Petr , Bjørklund Sunniva S. , Fleischer Thomas , Rob Lukas , Hruda Martin , Bouda Jiri , Mrhalova Marcela , Allah Mohammad Moufaq Khatar Al Obeed , Vodicka Pavel , Fiala Ondrej , Soucek Pavel , Kristensen Vessela N. , Vodickova Ludmila , Vaclavikova Radka 

TITLE=Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1016958

DOI=10.3389/fonc.2022.1016958

ISSN=2234-943X

ABSTRACT=<p>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 <italic>DUT</italic> expression with the presence of peritoneal metastases in EOC patients. The high-grade serous EOC subtype was enriched with <italic>TP53</italic> mutations compared to other subtypes. Furthermore, somatic mutations in <italic>XPC</italic> and <italic>PRKDC</italic> were significantly associated with worse overall survival of EOC patients, and higher <italic>FAAP20</italic> expression in platinum-resistant than platinum-sensitive patients was observed. We found higher methylation of <italic>RAD50</italic> in platinum-resistant than in platinum-sensitive patients. Somatic mutations in <italic>BRCA1</italic> and <italic>RAD9A</italic> were significantly associated with higher <italic>RBBP8</italic> 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.</p>