Department of Molecular Medicine (MOMA), Aarhus University Hospital (AUH), Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Department of Urology, Aarhus University Hospital (AUH), Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Int J Mol Sci. 2019 Mar 7;20(5):1173. doi: 10.3390/ijms20051173.
Prostate cancer (PCa) is a clinically heterogeneous disease and currently, accurate diagnostic and prognostic molecular biomarkers are lacking. This study aimed to identify novel DNA hypermethylation markers for PCa with future potential for blood-based testing. Accordingly, to search for genes specifically hypermethylated in PCa tissue samples and not in blood cells or other cancer tissue types, we performed a systematic analysis of genome-wide DNA methylation data (Infinium 450K array) available in the Marmal-aid database for 4072 malignant/normal tissue samples of various types. We identified eight top candidate markers (cg12799885, , , , , , , and ) that were specifically hypermethylated in PCa tissue samples and hypomethylated in other benign and malignant tissue types, including in peripheral blood cells. Potential as diagnostic and prognostic biomarkers was further assessed by the quantitative methylation specific PCR (qMSP) analysis of 37 nonmalignant and 197 PCa tissue samples from an independent population. Here, all eight hypermethylated candidates showed high sensitivity (75⁻94%) and specificity (84⁻100%) for PCa. Furthermore, , , and hypermethylation was significantly associated with biochemical recurrence (BCR) after radical prostatectomy (RP; 197 patients), independent of the routine clinicopathological variables. is the most promising single candidate marker (hazard ratio (HR) (95% confidence interval (CI)): 1.96 (1.24⁻3.10), adjusted = 0.016; multivariate cox regression). Further validation studies are warranted and should investigate the potential value of these hypermethylation candidate markers for blood-based testing also.
前列腺癌（PCa）是一种临床表现异质性疾病，目前缺乏准确的诊断和预后分子生物标志物。本研究旨在寻找用于 PCa 的新型 DNA 高甲基化标志物，以期未来能用于基于血液的检测。因此，为了寻找仅在 PCa 组织样本中而非在血细胞或其他癌症组织类型中高度甲基化的基因，我们对 Marmal-aid 数据库中 4072 种不同类型的恶性/正常组织样本的全基因组 DNA 甲基化数据（Infinium 450K 芯片）进行了系统分析。我们确定了 8 个候选的顶级标记物（cg12799885、、、、、、和），这些标记物仅在 PCa 组织样本中高度甲基化，而在其他良性和恶性组织类型中低甲基化，包括外周血细胞。通过对来自另一个独立人群的 37 个非恶性和 197 个 PCa 组织样本进行定量甲基化特异性 PCR（qMSP）分析，进一步评估了这些候选物作为诊断和预后生物标志物的潜力。在该分析中，所有 8 个高甲基化候选物对 PCa 均具有高灵敏度（75%至 94%）和高特异性（84%至 100%）。此外，、、和甲基化与根治性前列腺切除术后（RP；197 例患者）的生化复发（BCR）显著相关，与常规临床病理变量无关。是最有前途的单个候选标记物（风险比（HR）（95%置信区间（CI））：1.96（1.24⁻3.10），调整 = 0.016；多变量 cox 回归）。需要进一步的验证研究，并应调查这些高甲基化候选标记物用于基于血液的检测的潜在价值。
