ArticleClinical epigenetics2021
Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers.
Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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31 citing papers in PubMed, 43 citations in OpenAlex.
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Genome-Wide Assessment of DNA Methylation Fidelity Identifies Representative Ovarian Cancer Cell Line Models.Journal of cellular and molecular medicine · 2026Article
- Long-read, whole-genome sequencing and chemotherapy response of two patient-derived organoids from a TP53- and KRAS-mutant ovarian carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Targeting epigenetic networks to overcome cisplatin resistance in ovarian cancer: from mechanisms to clinical translation.Journal of ovarian research · 2026Review
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Genome-wide DNA methylation profiling reveals diagnostic markers in parathyroid tumours.Journal of endocrinological investigation · 2026Article
- Beta-Arrestin 1 Deficiency Enhances Host Anti-Myeloma Immunity Through T Cell Activation and Checkpoint Modulation.International journal of molecular sciences · 2025Article
- Global DNA methylation signatures associated with chemoresistance and poor prognosis of high grade serous ovarian cancer.Scientific reports · 2025Article
- Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients.HemaSphere · 2025Article
- Review
- Molecular classification of ovarian high-grade serous/endometrioid carcinomas through multi-omics analysis: JGOG3025-TR2 study.British journal of cancer · 2024Article
- Determination of platinum-resistance of women with ovarian cancer by FTIR spectroscopy combined with multivariate analyses and machine learning methods.Scientific reports · 2024Article
- Immune-related gene methylation prognostic instrument for stratification and targeted treatment of ovarian cancer patients toward advanced 3PM approach.The EPMA journal · 2024Article
- Chemo-small extracellular vesicles released in cisplatin-resistance ovarian cancer cells are regulated by the lysosomal function.Journal of extracellular biology · 2024Article
- Current data and future perspectives on DNA methylation in ovarian cancer (Review).International journal of oncology · 2024Review
- Validating reference-based algorithms to determine cell-type heterogeneity in ovarian cancer DNA methylation studies.Scientific reports · 2024Article
- Review
- Drug resistance in ovarian cancer: from mechanism to clinical trial.Molecular cancer · 2024Review
- Article
- Pancreatic Neuroendocrine Tumors: Signaling Pathways and Epigenetic Regulation.International journal of molecular sciences · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundIn contrast to stable genetic events, epigenetic changes are highly plastic and play crucial roles in tumor evolution and development. Epithelial ovarian cancer (EOC) is a highly heterogeneous disease that is generally associated with poor prognosis and treatment failure. Profiling epigenome-wide DNA methylation status is therefore essential to better characterize the impact of epigenetic alterations on the heterogeneity of EOC.
methodsAn epigenome-wide association study was conducted to evaluate global DNA methylation in a retrospective cohort of 80 mixed subtypes of primary ovarian cancers and 30 patients with high-grade serous ovarian carcinoma (HGSOC). Three demethylating agents, azacytidine, decitabine, and thioguanine, were tested their anti-cancer and anti-chemoresistant effects on HGSOC cells.
resultsGlobal DNA hypermethylation was significantly associated with high-grade tumors, platinum resistance, and poor prognosis. We determined that 9313 differentially methylated probes (DMPs) were enriched in their relative gene regions of 4938 genes involved in small GTPases and were significantly correlated with the PI3K-AKT, MAPK, RAS, and WNT oncogenic pathways. On the other hand, global DNA hypermethylation was preferentially associated with recurrent HGSOC. A total of 2969 DMPs corresponding to 1471 genes were involved in olfactory transduction, and calcium and cAMP signaling. Co-treatment with demethylating agents showed significant growth retardation in ovarian cancer cells through differential inductions, such as cell apoptosis by azacytidine or G2/M cell cycle arrest by decitabine and thioguanine. Notably, azacytidine and decitabine, though not thioguanine, synergistically enhanced cisplatin-mediated cytotoxicity in HGSOC cells.
conclusionsThis study demonstrates the significant association of global hypermethylation with poor prognosis and drug resistance in high-grade EOC and highlights the potential of demethylating agents in cancer treatment.
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