ArticleClinical epigenetics2018
Dysregulation and prognostic potential of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) levels in prostate cancer.
Article in Clinical epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Exploring the Role of DNA Methylation in the Epigenetic Landscape of Cancer.Biochemical genetics · 2026Review
- Relationship between Prostate Cancer and Benign Hyperplasia: Role of Inflammation-Induced Oxidative Stress, Vitamin C, and Epigenetics.The world journal of men's health · 2026Review
- Changes in active DNA demethylation pathway components during neoadjuvant chemotherapy and their prognostic significance in breast cancer.Breast cancer research : BCR · 2026Article
- Transcriptional and epigenetic reprogramming, lineage plasticity and therapy resistance in prostate cancer.Journal of the National Cancer Center · 2026Review
- TET1: The epigenetic architect of clinical disease progression.Genes & diseases · 2025Review
- Fundamentals of DNA methylation in development.Pediatric research · 2025Review
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
- Tracking Globally 5-Methylcytosine and Its Oxidized Derivatives in Colorectal Cancer Epigenome Using Bioelectroanalytical Technologies.ACS sensors · 2025Article
- Investigating the origins of the mutational signatures in cancer.Nucleic acids research · 2025Review
- Phytochemical synergies in BK002: advanced molecular docking insights for targeted prostate cancer therapy.Frontiers in pharmacology · 2025Review
- Shedding light on DNA methylation and its clinical implications: the impact of long-read-based nanopore technology.Epigenetics & chromatin · 2024Review
- Epigenetic DNA modifications and vitamin C in prostate cancer and benign prostatic hyperplasia: Exploring similarities, disparities, and pathogenic implications.Neoplasia (New York, N.Y.) · 2024Article
- Review
- TET3 downregulation and low 5-hydroxymethylcytosine are epigenetic signatures of head and neck carcinoma.Molecular biology reports · 2024Article
- A new methodology to reveal potential nucleic acid modifications associated with the risk of endometrial cancer through dispersive solid-phase extraction coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV.Analytical and bioanalytical chemistry · 2024Article
- The level of active DNA demethylation compounds in leukocytes and urine samples as potential epigenetic biomarkers in breast cancer patients.Scientific reports · 2024Article
- Inhibition of cytosine 5-hydroxymethylation during progression of cancer precursor lesions in the uterine cervix.PloS one · 2024Article
- Impact of antigen retrieval protocols on the immunohistochemical detection of epigenetic DNA modifications.Histochemistry and cell biology · 2023Article
- The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.Cancer research · 2022Article
- HPV infection and 5mC/5hmC epigenetic markers in penile squamous cell carcinoma: new insights into prognostics.Clinical epigenetics · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrognostic tools for prostate cancer (PC) are inadequate and new molecular biomarkers may improve risk stratification. The epigenetic mark 5-hydroxymethylcytosine (5hmC) has recently been proposed as a novel candidate prognostic biomarker in several malignancies including PC. 5hmC is an oxidized derivative of 5-methylcytosine (5mC) and can be further oxidized to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). The present study is the first to investigate the biomarker potential in PC for all four DNA methylation marks in parallel. Thus, we determined 5mC, 5hmC, 5fC, and 5caC levels in non-malignant (NM) and PC tissue samples from a large radical prostatectomy (RP) patient cohort (n = 546) by immunohistochemical (IHC) analysis of serial sections of a tissue microarray. Possible associations between methylation marks, routine clinicopathological parameters, ERG status, and biochemical recurrence (BCR) after RP were investigated.
results5mC and 5hmC levels were significantly reduced in PC compared to NM prostate tissue samples (p ≤ 0.027) due to a global loss of both marks specifically in ERG- PCs. 5fC levels were significantly increased in ERG+ PCs (p = 0.004), whereas 5caC levels were elevated in both ERG- and ERG+ PCs compared with NM prostate tissue samples (p ≤ 0.019). Positive correlations were observed between 5mC, 5fC, and 5caC levels in both NM and PC tissues (p < 0.001), while 5hmC levels were only weakly positively correlated to 5mC in the PC subset (p = 0.030). There were no significant associations between 5mC, 5fC, or ERG status and time to BCR in this RP cohort. In contrast, high 5hmC levels were associated with BCR in ERG- PCs (p = 0.043), while high 5caC levels were associated with favorable prognosis in ERG+ PCs (p = 0.011) and were borderline significantly associated with worse prognosis in ERG- PCs (p = 0.058). Moreover, a combined high-5hmC/high-5caC score was a significant adverse predictor of post-operative BCR beyond routine clinicopathological variables in ERG- PCs (hazard ratio 3.18 (1.54-6.56), p = 0.002, multivariate Cox regression).
conclusionsThis is the first comprehensive study of 5mC, 5hmC, 5fC, and 5caC levels in PC and the first report of a significant prognostic potential for 5caC in PC.
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