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Dysregulation and prognostic potential of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) levels in prostate cancer.


ABSTRACT: BACKGROUND:Prognostic 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. RESULTS:5mC 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?

SUBMITTER: Storebjerg TM 

PROVIDER: S-EPMC6081903 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Dysregulation and prognostic potential of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) levels in prostate cancer.

Storebjerg Tine Maj TM   Strand Siri H SH   Høyer Søren S   Lynnerup Anne-Sofie AS   Borre Michael M   Ørntoft Torben F TF   Sørensen Karina D KD  

Clinical epigenetics 20180807 1


<h4>Background</h4>Prognostic 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 po  ...[more]

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