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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

机译:5-甲基胞嘧啶(5mC)5-羟甲基胞嘧啶(5hmC)5-甲酰基胞嘧啶(5fC)和5-羧基胞嘧啶(5caC)水平在前列腺癌中的失调和预后潜力

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摘要

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.
机译:背景技术前列腺癌(PC)的预后工具不足,新的分子生物标记物可能会改善风险分层。表观遗传标记5-羟甲基胞嘧啶(5hmC)最近被提议作为包括PC在内的多种恶性肿瘤的新型候选预后生物标记。 5hmC是5-甲基胞嘧啶(5mC)的氧化衍生物,可以进一步氧化成5-甲酰基胞嘧啶(5fC)和5-羧基胞嘧啶(5caC)。本研究是第一个平行研究PC中所有四个DNA甲基化标记的生物标记物潜力的研究。因此,我们通过免疫组化(IHC)分析甲状旁腺的连续切片,确定了来自大型根治性前列腺切除术(RP)患者队列(n = 546)的非恶性(NM)和PC组织样本中的5mC,5hmC,5fC和5caC水平。组织芯片。研究了甲基化标记,常规临床病理参数,ERG状态和RP后生化复发(BCR)之间的可能关联。

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