Kachakova D, Mitkova A, Popov E, Beltcheva O, Vlahova A, Dikov T, Hristova S, Mitev V, Slavov C, Kaneva R
Department of Medical Chemistry and Biochemistry and Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria.
J BUON. 2013 Jul-Sep;18(3):660-8.
Searching for diagnostic and prognostic biomarkers for prostate cancer (PC) is main public health priority. DNA methylation in body fluids is a stable, easily detectable and promising PC biomarker. The major advantages of urine-based assays are their noninvasive nature and the ability to monitor PC with heterogeneous foci. The aim of this study was to determine the diagnostic value of the recently identified candidate PC biomarker HIST1H4K.
We investigated DNA methylation of HIST1H4K in urine samples from 57 PC patients, 29 controls with benign prostatic hyperplasia (BPH) and 50 young asymptomatic men (YAM) by MethyLight real-time PCR.
The frequency of HIST1H4K promoter hypermethylation significantly discriminated PC patients from YAM (AUC =0.763; 95% CI 0.672-0.839; p<0.0001), but did not show any statistical difference between PC patients and BPH controls (AUC=0.513, 95% CI 0.402-0.622; p=0.8255). HIST1H4K could not outperform the prostatic specific antigen (PSA) in our sample (AUC=0.785; 95% CI 0.679-0.870; p<0.0001). Methylation of HIST1H4K showed significant correlation with aging (r=0.5418; p<0.0001), but with no other clinicopathological characteristics.
The results suggest that the promoter hypermethylation of HIST1H4K is rather due to aging than related to prostate carcinogenesis. To elucidate this observation analysis of larger samples is needed.
寻找前列腺癌（PC）的诊断和预后生物标志物是主要的公共卫生优先事项。体液中的DNA甲基化是一种稳定、易于检测且有前景的PC生物标志物。基于尿液检测的主要优点是其非侵入性以及能够监测具有异质性病灶的PC。本研究的目的是确定最近鉴定出的候选PC生物标志物HIST1H4K的诊断价值。
我们通过甲基化荧光定量实时PCR研究了57例PC患者、29例良性前列腺增生（BPH）对照患者和50例年轻无症状男性（YAM）尿液样本中HIST1H4K的DNA甲基化情况。
HIST1H4K启动子高甲基化频率显著区分了PC患者与YAM（曲线下面积[AUC]=0.763；95%置信区间[CI]0.672 - 0.839；p<0.0001），但在PC患者和BPH对照之间未显示出任何统计学差异（AUC=0.513，95% CI 0.402 - 0.622；p=0.8255）。在我们的样本中，HIST1H4K的表现不如前列腺特异性抗原（PSA）（AUC=0.785；95% CI 0.679 - 0.870；p<0.0001）。HIST1H4K的甲基化与衰老显著相关（r=0.5418；p<0.0001），但与其他临床病理特征无关。
结果表明，HIST1H4K启动子高甲基化更多是由于衰老而非与前列腺癌发生相关。需要对更大样本进行分析以阐明这一观察结果。
