ArticleHuman molecular genetics2014
Hypomethylation signature of tumor-initiating cells predicts poor prognosis of ovarian cancer patients.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Hypermethylation of tumor suppressor genes is a risk factor for poor prognosis in ovarian cancer: A meta-analysis.Medicine · 2019Pooled it
- The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.Nutrition & metabolism · 2026Review
- Clinical validation of a DNA methylation biomarker associated with overall survival of relapsed ovarian cancer patients.International journal of cancer · 2026Article
- Ovarian Cancer Stem Cells: Mechanisms of Progression and Therapeutic Strategies.Oncology research · 2026Review
- Autophagy Protease ATG4D Facilitates Proliferation and Malignancy of Osteosarcoma Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Autophagy mediated immune response regulation and drug resistance in cancer.Molecular biology reports · 2025Review
- Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.Current issues in molecular biology · 2024Review
- mBMC cancer · 2024Article
- A review on regulation of DNA methylation during post-myocardial infarction.Frontiers in pharmacology · 2024Review
- Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Cancer cells same as zombies reprogram normal cells via the secreted microenvironment.PloS one · 2023Article
- Distinct promotor methylation at tumor suppressive genes in ovarian cancer stromal progenitor cells and ovarian cancer and its clinical implication.American journal of cancer research · 2022Article
- Role of Circulating Biomarkers in Platinum-Resistant Ovarian Cancer.International journal of molecular sciences · 2021Review
- A new prognostic risk model based on autophagy-related genes in kidney renal clear cell carcinoma.Bioengineered · 2021Article
- HIST1H2BN induced cell proliferation and EMT phenotype in prostate cancer via NF-κB signal pathway.Genes & genomics · 2021Article
- DNA transposons mediate duplications via transposition-independent and -dependent mechanisms in metazoans.Nature communications · 2021Article
- Epigenetic regulation of autophagy: A key modification in cancer cells and cancer stem cells.World journal of stem cells · 2021Review
- An Autophagy-Related Long Non-Coding RNA Prognostic Signature for Patients with Lung Squamous Carcinoma Based on Bioinformatics Analysis.International journal of general medicine · 2021Article
- Prognostic Signature of Osteosarcoma Based on 14 Autophagy-Related Genes.Pathology oncology research : POR · 2021Article
- Global DNA Hypomethylation in Epithelial Ovarian Cancer: Passive Demethylation and Association with Genomic Instability.Cancers · 2020Article
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
DNA methylation contributes to tumor formation, development and metastasis. Epigenetic dysregulation of stem cells is thought to predispose to malignant development. The clinical significance of DNA methylation in ovarian tumor-initiating cells (OTICs) remains unexplored. We analyzed the methylomic profiles of OTICs (CP70sps) and their derived progeny using a human methylation array. qRT-PCR, quantitative methylation-specific PCR (qMSP) and pyrosequencing were used to verify gene expression and DNA methylation in cancer cell lines. The methylation status of genes was validated quantitatively in cancer tissues and correlated with clinicopathological factors. ATG4A and HIST1H2BN were hypomethylated in OTICs. Methylation analysis of ATG4A and HIST1H2BN by qMSP in 168 tissue samples from patients with ovarian cancer showed that HIST1H2BN methylation was a significant and independent predictor of progression-free survival (PFS) and overall survival (OS). Multivariate Cox regression analysis showed that patients with a low level of HIST1H2BN methylation had poor PFS (hazard ratio (HR), 4.5; 95% confidence interval (CI), 1.4-14.8) and OS (HR, 4.3; 95% CI, 1.3-14.0). Hypomethylation of both ATG4A and HIST1H2BN predicted a poor PFS (HR, 1.8; 95% CI, 1.0-3.6; median, 21 months) and OS (HR, 1.7; 95% CI, 1.0-3.0; median, 40 months). In an independent cohort of ovarian tumors, hypomethylation predicted early disease recurrence (HR, 1.7; 95% CI, 1.1-2.5) and death (HR, 1.4; 95% CI, 1.0-1.9). The demonstration that expression of ATG4A in cells increased their stem properties provided an indication of its biological function. Hypomethylation of ATG4A and HIST1H2BN in OTICs predicts a poor prognosis for ovarian cancer patients.
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