ArticleEpigenetics2013
Comprehensive methylome analysis of ovarian tumors reveals hedgehog signaling pathway regulators as prognostic DNA methylation biomarkers.
Article in Epigenetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- The multifaceted roles of ZIC genes in cancer: from development regulators to cancer modulators.Discover oncology · 2025Review
- The Diversity of Methylation Patterns in Serous Borderline Ovarian Tumors and Serous Ovarian Carcinomas.Cancers · 2024Article
- Epigenetic silencing of ZIC4 unveils a potential tumor suppressor role in pediatric choroid plexus carcinoma.Scientific reports · 2024Article
- miRNA: A Promising Therapeutic Target in Cancer.International journal of molecular sciences · 2022Review
- Age-Related DNA Methylation in Normal Kidney Tissue Identifies Epigenetic Cancer Risk Susceptibility Loci in the ANKRD34B and ZIC1 Genes.International journal of molecular sciences · 2022Article
- DNA methylation marker to estimate ovarian cancer cell fraction.Medical oncology (Northwood, London, England) · 2022Article
- Accurate Prediction of Prognosis by Integrating Clinical and Molecular Characteristics in Colon Cancer.Frontiers in cell and developmental biology · 2021Article
- The Hedgehog signaling pathway promotes chemotherapy resistance via multidrug resistance protein 1 in ovarian cancer.Oncology reports · 2020Article
- Expression and clinical significance of methyl-CpG binding domain protein 2 in high-grade serous ovarian cancer.Oncology letters · 2020Article
- Ovarian cancer detection by DNA methylation in cervical scrapings.Clinical epigenetics · 2019Article
- Epigenetic activation of POTE genes in ovarian cancer.Epigenetics · 2019Article
- Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives.Frontiers in cell and developmental biology · 2019Review
- Epigenetics in ovarian cancer.Seminars in cancer biology · 2018Review
- Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors.International journal of cancer · 2018Article
- Clinicopathologic and Prognostic Significance of the Zinc Finger of the Cerebellum Family in Invasive Breast Cancer.Journal of breast cancer · 2018Article
- Aberrant methylation of PCDH17 gene in high-grade serous ovarian carcinoma.Cancer biomarkers : section A of Disease markers · 2018Article
- Methylomics of nitroxidative stress on precancerous cells reveals DNA methylation alteration at the transition fromOncotarget · 2017Article
- An epigenetic signature of adhesion molecules predicts poor prognosis of ovarian cancer patients.Oncotarget · 2017Article
- Methylome analysis of extreme chemoresponsive patients identifies novel markers of platinum sensitivity in high-grade serous ovarian cancer.BMC medicine · 2017Article
- Tripartite Motif 16 Inhibits the Migration and Invasion in Ovarian Cancer Cells.Oncology research · 2017Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 3 countries.
Funding
Abstract
Women with advanced stage ovarian cancer (OC) have a five-year survival rate of less than 25%. OC progression is associated with accumulation of epigenetic alterations and aberrant DNA methylation in gene promoters acts as an inactivating "hit" during OC initiation and progression. Abnormal DNA methylation in OC has been used to predict disease outcome and therapy response. To globally examine DNA methylation in OC, we used next-generation sequencing technology, MethylCap-sequencing, to screen 75 malignant and 26 normal or benign ovarian tissues. Differential DNA methylation regions (DMRs) were identified, and the Kaplan-Meier method and Cox proportional hazard model were used to correlate methylation with clinical endpoints. Functional role of specific genes identified by MethylCap-sequencing was examined in in vitro assays. We identified 577 DMRs that distinguished (p < 0.001) malignant from non-malignant ovarian tissues; of these, 63 DMRs correlated (p < 0.001) with poor progression free survival (PFS). Concordant hypermethylation and corresponding gene silencing of sonic hedgehog pathway members ZIC1 and ZIC4 in OC tumors was confirmed in a panel of OC cell lines, and ZIC1 and ZIC4 repression correlated with increased proliferation, migration and invasion. ZIC1 promoter hypermethylation correlated (p < 0.01) with poor PFS. In summary, we identified functional DNA methylation biomarkers significantly associated with clinical outcome in OC and suggest our comprehensive methylome analysis has significant translational potential for guiding the design of future clinical investigations targeting the OC epigenome. Methylation of ZIC1, a putative tumor suppressor, may be a novel determinant of OC outcome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.