Introduction/Background Ovarian cancer is characterized by a high mortality rate, common resistance to treatment and subsequent relapse. The objective of this study was to pinpoint the molecular characteristics associated with resistance to chemotherapy, focusing particularly on the unfavorable prognosis of patients, with special attention to the serous high-grade subtype.

Methodology The whole transcriptome profile was assessed using RNA sequencing in a cohort of 60 patients with epithelial ovarian cancer (EOC) characterized by their platinum-resistant status. Within a subgroup of 50 EOC patients, whole exome sequencing was conducted on matched pairs of tumor tissue and blood samples.

Results Differential expression analysis showed numerous significant results, the biggest expression difference was observed between HGSC and clear-cell subtype (< 200 genes), grade 1 vs. grade 3 (< 80 genes), residuum after surgery (< 60 genes), presence of variants characterized as MODERATE in TP53 gene (< 500 genes), germline variants in BRCA1 (< 60 genes), oppositely presence of germline variants in BRCA2 showed no significant changes in gene expression, PABPC1 HIGH impact variants (< 30 genes). In addition, EOC tumors resistant to platinum-based therapy demonstrate a notably elevated number of somatic TP53 mutations and fewer mutations in the Hippo pathway genes in comparison with those with favorable therapy response. Crucial involvement of somatic mutations in genes related to homologous recombination in predicting resistance and their correlation with positive patient prognosis was also found.

Conclusion Focusing on transcriptome profile analysis based on somatic/germline variants showed numerous differentially expressed genes. Analysis of molecular profile showed significant mutations in TP53 gene, Hippo pathway and many other genes involved in DNA repair system. Supported by the Czech Health Research Council grant no. NU22–08-00186 and Cooperatio program no. 207035, ‘Maternal and Childhood Care’ by 3rd Faculty Medicine, Charles University.

Disclosures This study was supported by running projects of the Czech Health Research Council grant no. NV22–08-00186 and Cooperatio program no. 207035, ‘Maternal and Childhood Care’ by 3rd Faculty Medicine, Charles University.