Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark.
Int J Mol Sci. 2019 Feb 27;20(5):1025. doi: 10.3390/ijms20051025.
This study aimed to validate whether 5-hydroxymethylcytosine (5hmC) level in combination with ERG expression is a predictive biomarker for biochemical failure (BF) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa). The study included 592 PCa patients from two consecutive Danish RP cohorts. 5hmC level and ERG expression were analyzed using immunohistochemistry in RP specimens. 5hmC was scored as low or high and ERG was scored as negative or positive. Risk of BF was analyzed using stratified cumulative incidences and multiple cause-specific Cox regression using competing risk assessment. Median follow-up was 10 years (95% CI: 9.5⁻10.2). In total, 246 patients (41.6%) had low and 346 patients (58.4%) had high 5hmC level. No significant association was found between 5hmC level or ERG expression and time to BF ( = 0.2 and = 1.0, respectively). However, for men with ERG negative tumors, high 5hmC level was associated with increased risk of BF following RP ( = 0.01). In multiple cause-specific Cox regression analyses of ERG negative patients, high 5hmC expression was associated with time to BF (HR: 1.8; 95% CI: 1.2⁻2.7; = 0.003). In conclusion, high 5hmC level was correlated with time to BF in men with ERG negative PCa, which is in accordance with previous results.
本研究旨在验证 5-羟甲基胞嘧啶（5hmC）水平与 ERG 表达相结合是否可作为接受根治性前列腺切除术（RP）治疗前列腺癌（PCa）的男性发生生化失败（BF）的预测生物标志物。该研究纳入了来自两个连续的丹麦 RP 队列的 592 例 PCa 患者。RP 标本中采用免疫组织化学法检测 5hmC 水平和 ERG 表达。5hmC 评分分为低或高，ERG 评分分为阴性或阳性。使用分层累积发生率和多因素特异性 Cox 回归分析（基于竞争风险评估）分析 BF 风险。中位随访时间为 10 年（95%CI：9.5⁻10.2）。共有 246 例（41.6%）患者的 5hmC 水平较低，346 例（58.4%）患者的 5hmC 水平较高。5hmC 水平或 ERG 表达与 BF 时间之间未发现显著相关性（ = 0.2 和 = 1.0）。然而，对于 ERG 阴性肿瘤患者，高 5hmC 水平与 RP 后 BF 风险增加相关（ = 0.01）。在 ERG 阴性患者的多因素特异性 Cox 回归分析中，高 5hmC 表达与 BF 时间相关（HR：1.8；95%CI：1.2⁻2.7； = 0.003）。总之，在 ERG 阴性 PCa 男性中，高 5hmC 水平与 BF 时间相关，这与之前的结果一致。
