Research Article


DOI :10.26650/experimed.1491074   IUP :10.26650/experimed.1491074    Full Text (PDF)

Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers

Tuğçe Şentürk KırmızıtaşServet TunoğluJean HelmijrSamet TopuzMaurice JansenTuba Günel

Objective: Identification of methylation patterns in cell-free DNA (cfDNA) provides a non-invasive methodology for discovering critical biomarkers that facilitate detection and prognostic evaluation of ovarian cancer (OC). This study explored the epigenetic landscape of OC by examining the DNA methylation patterns of cfDNA. Materials and Methods: Plasma samples from 5 OC patients and 5 healthy blood donors (HBDs) were processed for cfDNA isolation and methylated DNA immunoprecipitation, followed by next-generation sequencing and bioinformatics analysis to identify differentially methylated regions (DMRs) and genes (DMGs). Integration with The Cancer Genome Atlas (TCGA) data identified differentially expressed genes (DEGs) for functional analysis.

Results: The analysis revealed significant alterations in DNA methylation patterns, with 62 hypermethylated and 2 hypomethylated DMRs in OC compared with HBDs. Hierarchical clustering revealed distinct methylation patterns between OC and HBDs. Integrative analysis identified 18 genes with overlapping methylation and expression changes in OC and a negative correlation between methylation and expression levels (p<0.05). Ten genes exhibited a hypermethylation-downregulation pattern, indicating a suppressive role, whereas eight showed hypermethylation-upregulation. Survival analysis of OC data from TCGA highlighted B3GNT3 (p=0.04) and LRP1B (p=0.053) as promising prognostic markers.

Conclusion: Our study revealed an intricate relationship between DNA methylation alterations and gene expression dysregulation in ovarian cancer. We found that hypermethylation of B3GNT3 was correlated with its upregulation and poor survival outcomes, whereas hypermethylation of LRP1B pointed to its role as a tumor suppressor gene. 


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References

  • 1. Feng J, Xu L, Chen Y, Lin R, Li H, He H. Trends in incidence and mortality for ovarian cancer in China from 1990 to 2019 and its forecasted levels in 30 years. J Ovarian Res 2023; 16(1): 139. google scholar
  • 2. Balla A, Bhak J, Biro O. The application of circulating tumor cell and cell-free DNA liquid biopsies in ovarian cancer. Mol Cell Probes 2022; 66: 101871. google scholar
  • 3. Hinchcliff E, Westin SN, Herzog TJ. State of the science: contemporary front-line treatment of advanced ovarian cancer. Gynecol Oncol 2022; 166(1): 18-24. google scholar
  • 4. Roque R, Ribeiro IP, Figueiredo-Dias M, Gourley C, Carreira IM. Current applications and challenges of next-generation sequencing in plasma circulating tumor DNA of ovarian cancer. Biology 2024; 13(2): 88. google scholar
  • 5. Giannopoulou L, Mastoraki S, Buderath P, Strati A, Pavlakis K, Kasimir-Bauer S, et al. ESR1 methylation in primary tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer. Gynecol Oncol 2018; 150(2): 355-60. google scholar
  • 6. Lu H, Liu Y, Wang J, Fu S, Wang L, Huang C, et al. Detection of ovarian cancer using plasma cell-free DNA methylomes. Clin Epigenetics 2022; 14(1): 74. google scholar
  • 7. Margolin G, Petrykowska HM, Athamanolap P, Goncearenco A, Osei-Tutu A, Annunziata CM, et al. Leveraging locus-specific epigenetic heterogeneity to improve the performance of blood-based DNA methylation biomarkers. Clin Epigenetics 2020; 12: 154. google scholar
  • 8. Marinelli LM, Kisiel JB, Slettedahl SW, Mahoney DW, Lemens MA, Shridhar V, et al. Methylated DNA markers for plasma detection of ovarian cancer: discovery, validation, and clinical feasibility. Gynecol Oncol 2022; 165(3): 568-76. google scholar
  • 9. Peng S, Zhang X, Wu Y. Potential applications of DNA methylation testing technology in female tumors and screening methods. Biochim Biophys Acta Rev Cancer 2023; 1878(5): 188941. google scholar
  • 10. Papanicolau-Sengos A, Aldape K. DNA methylation profiling: an emerging paradigm for cancer diagnosis. Annu Rev Pathol 2022; 17: 295-321. google scholar
  • 11. Asante D-B, Calapre L, Ziman M, Meniawy TM, Gray ES. Liquid biopsy in ovarian cancer using circulating tumor DNA and cells: ready for prime time? Cancer Lett 2020; 468: 59-71. google scholar
  • 12. Govindarajan M, Wohlmuth C, Waas M, Bernardini MQ, Kislinger T. High-throughput approaches for precision medicine in high-grade serous ovarian cancer. J Hematol Oncol 2020; 13: 1-20. google scholar
  • 13. Sanchez-Herrero E, Serna-Blasco R, Robado de Lope L, Gonzalez-Rumayor V, Romero A, Provencio M. Circulating tumor DNA as a cancer biomarker: an overview of biological features and factors that may impact on ctDNA analysis. Front Oncol 2022; 12: 943253. google scholar
  • 14. Li Y, Fan Z, Meng Y, Liu S, Zhan H. Blood-based DNA methylation signatures in cancer: a systematic review. Biochim Biophys Acta Mol Basis Dis 2023; 1869(1): 166583. google scholar
  • 15. Taiwo O, Wilson GA, Morris T, Seisenberger S, Reik W, Pearce D, et al. Methylome analysis using MeDIP-seq with low DNA concentrations. Nat Protoc 2012; 7(4): 617-36. google scholar
  • 16. Geissler F, Nesic K, Kondrashova O, Dobrovic A, Swisher EM, Scott CL, et al. The role of aberrant DNA methylation in cancer initiation and clinical impacts. Ther Adv Med Oncol 2024; 16: 17588359231220511. google scholar
  • 17. Chen YC, Elnitski L. Aberrant DNA methylation defines isoform usage in cancer, with functional implications. PLoS Comput Biol 2019; 15(7): e1007095. google scholar
  • 18. Rini BI, Zhang J, Hall O, Bergener J, Wang Y, Brown B, et al. 1910P evaluation of a genome-wide methylome enrichment platform for circulating tumor DNA quantification and prognostic performance in renal cell carcinoma (RCC). Ann Oncol 2023; 34: S1028. google scholar
  • 19. Rauluseviciute I, Drabl0s F, Rye MB. DNA hypermethylation associated with upregulated gene expression in prostate cancer demonstrates the diversity of epigenetic regulation. BMC Med Genomics 2020; 13(1): 6. google scholar
  • 20. Ren X, Lin S, Guan F, Kang H. Glycosylation targeting: a paradigm shift in cancer immunotherapy. Int J Biol Sci 2024; 20(7): 2607-21. google scholar
  • 21. Leng X, Wei S, Mei J, Deng S, Yang Z, Liu Z, et al. Identifying the prognostic significance of B3GNT3 with PD-L1 expression in lung adenocarcinoma. Transl Lung Cancer Res 2021; 10(2): 965. google scholar
  • 22. Xu J, Guo Z, Yuan S, Li H, Luo S. Upregulation of B3GNT3 is associated with immune infiltration and activation of NF-kB pathway in gynecologic cancers. J Reprod Immunol 2022; 152: 103658. google scholar
  • 23. Pnncipe C, Dionı'sio de Sousa IJ, Prazeres H, Soares P, Lima RT. LRP1B: a giant lost in cancer translation. Pharmaceuticals 2021; 14(9): 836. google scholar
  • 24. Cowin PA, George J, Fereday S, Loehrer E, Van Loo P, Cullinane C, et al. LRP1B deletion in high-grade serous ovarian cancers is associated with acquired chemotherapy resistance to liposomal doxorubicin. Cancer Res 2012; 72(16): 4060-73. google scholar

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APA

Kırmızıtaş, T.Ş., Tunoğlu, S., Helmijr, J., Topuz, S., Jansen, M., & Günel, T. (2024). Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers. Experimed, 14(3), 161-173. https://doi.org/10.26650/experimed.1491074


AMA

Kırmızıtaş T Ş, Tunoğlu S, Helmijr J, Topuz S, Jansen M, Günel T. Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers. Experimed. 2024;14(3):161-173. https://doi.org/10.26650/experimed.1491074


ABNT

Kırmızıtaş, T.Ş.; Tunoğlu, S.; Helmijr, J.; Topuz, S.; Jansen, M.; Günel, T. Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers. Experimed, [Publisher Location], v. 14, n. 3, p. 161-173, 2024.


Chicago: Author-Date Style

Kırmızıtaş, Tuğçe Şentürk, and Servet Tunoğlu and Jean Helmijr and Samet Topuz and Maurice Jansen and Tuba Günel. 2024. “Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers.” Experimed 14, no. 3: 161-173. https://doi.org/10.26650/experimed.1491074


Chicago: Humanities Style

Kırmızıtaş, Tuğçe Şentürk, and Servet Tunoğlu and Jean Helmijr and Samet Topuz and Maurice Jansen and Tuba Günel. Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers.” Experimed 14, no. 3 (Dec. 2024): 161-173. https://doi.org/10.26650/experimed.1491074


Harvard: Australian Style

Kırmızıtaş, TŞ & Tunoğlu, S & Helmijr, J & Topuz, S & Jansen, M & Günel, T 2024, 'Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers', Experimed, vol. 14, no. 3, pp. 161-173, viewed 21 Dec. 2024, https://doi.org/10.26650/experimed.1491074


Harvard: Author-Date Style

Kırmızıtaş, T.Ş. and Tunoğlu, S. and Helmijr, J. and Topuz, S. and Jansen, M. and Günel, T. (2024) ‘Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers’, Experimed, 14(3), pp. 161-173. https://doi.org/10.26650/experimed.1491074 (21 Dec. 2024).


MLA

Kırmızıtaş, Tuğçe Şentürk, and Servet Tunoğlu and Jean Helmijr and Samet Topuz and Maurice Jansen and Tuba Günel. Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers.” Experimed, vol. 14, no. 3, 2024, pp. 161-173. [Database Container], https://doi.org/10.26650/experimed.1491074


Vancouver

Kırmızıtaş TŞ, Tunoğlu S, Helmijr J, Topuz S, Jansen M, Günel T. Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers. Experimed [Internet]. 21 Dec. 2024 [cited 21 Dec. 2024];14(3):161-173. Available from: https://doi.org/10.26650/experimed.1491074 doi: 10.26650/experimed.1491074


ISNAD

Kırmızıtaş, TuğçeŞentürk - Tunoğlu, Servet - Helmijr, Jean - Topuz, Samet - Jansen, Maurice - Günel, Tuba. Epigenetic Signatures in Ovarian Cancer to Determine Potential Diagnostic/Prognostic Biomarkers”. Experimed 14/3 (Dec. 2024): 161-173. https://doi.org/10.26650/experimed.1491074



TIMELINE


Submitted28.05.2024
Accepted06.08.2024
Published Online19.12.2024

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