Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy
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 t...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1016958/full |
| _version_ | 1811316467442909184 |
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| author | Karolina Seborova Karolina Seborova Viktor Hlavac Viktor Hlavac Petr Holy Petr Holy Petr Holy Sunniva S. Bjørklund Thomas Fleischer Lukas Rob Martin Hruda Jiri Bouda Marcela Mrhalova Mohammad Moufaq Khatar Al Obeed Allah Pavel Vodicka Pavel Vodicka Pavel Vodicka Ondrej Fiala Ondrej Fiala Pavel Soucek Pavel Soucek Vessela N. Kristensen Ludmila Vodickova Ludmila Vodickova Ludmila Vodickova Radka Vaclavikova Radka Vaclavikova |
| author_facet | Karolina Seborova Karolina Seborova Viktor Hlavac Viktor Hlavac Petr Holy Petr Holy Petr Holy Sunniva S. Bjørklund Thomas Fleischer Lukas Rob Martin Hruda Jiri Bouda Marcela Mrhalova Mohammad Moufaq Khatar Al Obeed Allah Pavel Vodicka Pavel Vodicka Pavel Vodicka Ondrej Fiala Ondrej Fiala Pavel Soucek Pavel Soucek Vessela N. Kristensen Ludmila Vodickova Ludmila Vodickova Ludmila Vodickova Radka Vaclavikova Radka Vaclavikova |
| author_sort | Karolina Seborova |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:50:28Z |
| format | Article |
| id | doaj.art-4d3c2d1b733a4311bfac5bc44475ebba |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T11:50:28Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4d3c2d1b733a4311bfac5bc44475ebba2022-12-22T02:48:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-12-011210.3389/fonc.2022.10169581016958Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapyKarolina Seborova0Karolina Seborova1Viktor Hlavac2Viktor Hlavac3Petr Holy4Petr Holy5Petr Holy6Sunniva S. Bjørklund7Thomas Fleischer8Lukas Rob9Martin Hruda10Jiri Bouda11Marcela Mrhalova12Mohammad Moufaq Khatar Al Obeed Allah13Pavel Vodicka14Pavel Vodicka15Pavel Vodicka16Ondrej Fiala17Ondrej Fiala18Pavel Soucek19Pavel Soucek20Vessela N. Kristensen21Ludmila Vodickova22Ludmila Vodickova23Ludmila Vodickova24Radka Vaclavikova25Radka Vaclavikova26Toxicogenomics Unit, National Institute of Public Health in Prague, Prague, CzechiaBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaToxicogenomics Unit, National Institute of Public Health in Prague, Prague, CzechiaBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaToxicogenomics Unit, National Institute of Public Health in Prague, Prague, CzechiaBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaThird Faculty of Medicine, Charles University, Prague, CzechiaDepartment of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, NorwayDepartment of Gynecology and Obstetrics, Third Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, CzechiaDepartment of Gynecology and Obstetrics, Third Faculty of Medicine and University Hospital Kralovske Vinohrady, Prague, CzechiaDepartment of Gynecology and Obstetrics, University Hospital in Pilsen, Charles University, Pilsen, CzechiaDepartment of Pathology and Molecular Medicine, Motol University Hospital, Second Faculty of Medicine, Charles University, Prague, CzechiaBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaInstitute of Experimental Medicine, Czech Academy of Sciences, Prague, Czechia0Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czechia1Department of Oncology and Radiotherapeutics, Faculty of Medicine in Pilsen and University Hospital, Charles University, Pilsen, Czechia2Laboratory of Cancer Treatment and Tissue Regeneration, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaToxicogenomics Unit, National Institute of Public Health in Prague, Prague, CzechiaBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaDepartment of Medical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaInstitute of Experimental Medicine, Czech Academy of Sciences, Prague, Czechia0Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, CzechiaToxicogenomics Unit, National Institute of Public Health in Prague, Prague, CzechiaBiomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, CzechiaEpithelial 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.1016958/fullovarian carcinomaDNA repair genesresistancetranscriptomemethylomewhole exome sequencing |
| spellingShingle | Karolina Seborova Karolina Seborova Viktor Hlavac Viktor Hlavac Petr Holy Petr Holy Petr Holy Sunniva S. Bjørklund Thomas Fleischer Lukas Rob Martin Hruda Jiri Bouda Marcela Mrhalova Mohammad Moufaq Khatar Al Obeed Allah Pavel Vodicka Pavel Vodicka Pavel Vodicka Ondrej Fiala Ondrej Fiala Pavel Soucek Pavel Soucek Vessela N. Kristensen Ludmila Vodickova Ludmila Vodickova Ludmila Vodickova Radka Vaclavikova Radka Vaclavikova Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy Frontiers in Oncology ovarian carcinoma DNA repair genes resistance transcriptome methylome whole exome sequencing |
| title | Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy |
| title_full | Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy |
| title_fullStr | Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy |
| title_full_unstemmed | Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy |
| title_short | Complex molecular profile of DNA repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum-based therapy |
| title_sort | complex molecular profile of dna repair genes in epithelial ovarian carcinoma patients with different sensitivity to platinum based therapy |
| topic | ovarian carcinoma DNA repair genes resistance transcriptome methylome whole exome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1016958/full |
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