Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma
Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, its recurrence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with an ominous prognosis and chemotherapy resistance, but the role of DNA methyltransferases (D...
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MDPI AG
2023-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/20/4950 |
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| author | Efthymia Papakonstantinou Ioanna Pappa Georgios Androutsopoulos Georgios Adonakis Ioannis Maroulis Vasiliki Tzelepi |
| author_facet | Efthymia Papakonstantinou Ioanna Pappa Georgios Androutsopoulos Georgios Adonakis Ioannis Maroulis Vasiliki Tzelepi |
| author_sort | Efthymia Papakonstantinou |
| collection | DOAJ |
| description | Background: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, its recurrence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with an ominous prognosis and chemotherapy resistance, but the role of DNA methyltransferases (DNMTs) in EOC remains to be investigated. Methods: In the current study, we systematically retrieved gene expression data from patients with EOC and studied the immunohistochemical expression of DNMTs in 108 primary and 26 relapsed tumors. Results: Our results showed that the DNMT1, DNMT3A, DNMT3B and DNMT3L RNA levels were higher and the DNMT2 level was lower in tumors compared to non-neoplastic tissue, and DNMT3A and DNMT2 expression decreased from Stage-II to Stage-IV carcinomas. The proteomic data also suggested that the DNMT1 and DNMT3A levels were increased in the tumors. Similarly, the DNMT1, DNMT3A and DNMT3L protein levels were overexpressed and DNMT2 expression was reduced in high-grade carcinomas compared to non-neoplastic tissue and low-grade tumors. Moreover, DNMT1 and DNMT3L were increased in relapsed tumors compared to their primaries. The DNMT3A, DNMT1 and DNMT3B mRNA levels were correlated with overall survival. Conclusions: Our study demonstrates that DNMT1 and DNMT3L are upregulated in primary high-grade EOC and further increase in relapses, whereas DNMT3A is upregulated only in the earlier stages of cancer progression. DNMT2 downregulation highlights the presumed tumor-suppressor activity of this gene in ovarian carcinoma. |
| first_indexed | 2024-03-10T21:22:41Z |
| format | Article |
| id | doaj.art-8ee163a5030f4dd28ea1141861c7f754 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:22:41Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8ee163a5030f4dd28ea1141861c7f7542023-11-19T15:58:25ZengMDPI AGCancers2072-66942023-10-011520495010.3390/cancers15204950Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian CarcinomaEfthymia Papakonstantinou0Ioanna Pappa1Georgios Androutsopoulos2Georgios Adonakis3Ioannis Maroulis4Vasiliki Tzelepi5Department of Obstetrics and Gynecology, School of Medicine, University of Patras, 26504 Patras, GreeceMultidimensional Data Analysis and Knowledge Management Laboratory, Computer Engineering and Informatics Department, School of Engineering, University of Patras, 26504 Patras, GreeceGynecological Oncology Unit, Department of Obstetrics and Gynecology, Medical School, University of Patras, 26504 Patras, GreeceDepartment of Obstetrics and Gynecology, School of Medicine, University of Patras, 26504 Patras, GreeceDepartment of General Surgery, School of Medicine, University of Patras, 26504 Patras, GreeceDepartment of Pathology, School of Medicine, University of Patras, 26504 Patras, GreeceBackground: Despite recent advances in epithelial ovarian carcinoma (EOC) treatment, its recurrence and mortality rates have not improved significantly. DNA hypermethylation has generally been associated with an ominous prognosis and chemotherapy resistance, but the role of DNA methyltransferases (DNMTs) in EOC remains to be investigated. Methods: In the current study, we systematically retrieved gene expression data from patients with EOC and studied the immunohistochemical expression of DNMTs in 108 primary and 26 relapsed tumors. Results: Our results showed that the DNMT1, DNMT3A, DNMT3B and DNMT3L RNA levels were higher and the DNMT2 level was lower in tumors compared to non-neoplastic tissue, and DNMT3A and DNMT2 expression decreased from Stage-II to Stage-IV carcinomas. The proteomic data also suggested that the DNMT1 and DNMT3A levels were increased in the tumors. Similarly, the DNMT1, DNMT3A and DNMT3L protein levels were overexpressed and DNMT2 expression was reduced in high-grade carcinomas compared to non-neoplastic tissue and low-grade tumors. Moreover, DNMT1 and DNMT3L were increased in relapsed tumors compared to their primaries. The DNMT3A, DNMT1 and DNMT3B mRNA levels were correlated with overall survival. Conclusions: Our study demonstrates that DNMT1 and DNMT3L are upregulated in primary high-grade EOC and further increase in relapses, whereas DNMT3A is upregulated only in the earlier stages of cancer progression. DNMT2 downregulation highlights the presumed tumor-suppressor activity of this gene in ovarian carcinoma.https://www.mdpi.com/2072-6694/15/20/4950DNA methylationDNA methyltransferasesDNMTovarian cancerhigh-grade ovarian cancerrelapsed ovarian cancer |
| spellingShingle | Efthymia Papakonstantinou Ioanna Pappa Georgios Androutsopoulos Georgios Adonakis Ioannis Maroulis Vasiliki Tzelepi Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma Cancers DNA methylation DNA methyltransferases DNMT ovarian cancer high-grade ovarian cancer relapsed ovarian cancer |
| title | Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma |
| title_full | Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma |
| title_fullStr | Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma |
| title_full_unstemmed | Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma |
| title_short | Comprehensive Analysis of DNA Methyltransferases Expression in Primary and Relapsed Ovarian Carcinoma |
| title_sort | comprehensive analysis of dna methyltransferases expression in primary and relapsed ovarian carcinoma |
| topic | DNA methylation DNA methyltransferases DNMT ovarian cancer high-grade ovarian cancer relapsed ovarian cancer |
| url | https://www.mdpi.com/2072-6694/15/20/4950 |
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