Department of Clinical Biochemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz 85-092, Poland.
Department of Urology, Jan Biziel University Hospital, Bydgoszcz 85-168; Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Poland.
Neoplasia. 2024 Dec;58:101079. doi: 10.1016/j.neo.2024.101079. Epub 2024 Oct 29.
Benign Prostatic Hyperplasia (BPH) and Prostate Cancer (PC) are very common pathologies among aging men. Both disorders involve aberrant cell division and differentiation within the prostate gland. However, the direct link between these two disorders still remains controversial. A plethora of works have demonstrated that inflammation is a major causative factor in both pathologies. Another key factor involved in PC development is DNA methylation and hydroxymethylation.
A broad spectrum of parameters, including epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine, was analyzed by two-dimensional ultraperformance liquid chromatography with tandem mass spectrometry in tissues of BPH, PC, and marginal one, as well as in leukocytes of the patients and the control group. In the same material, the expression of TETs and TDG genes was measured using RT-qPCR. Additionally, vitamin C was quantified in the blood plasma and within cells (leukocytes and prostate tissues).
Unique patterns of DNA modifications and intracellular vitamin C (iVC) in BPH and PC tissues, as well as in leukocytes, were found in comparison with control samples. The majority of the alterations were more pronounced in leukocytes than in the prostate tissues.
Characteristic DNA methylation/hydroxymethylation and iVC profiles have been observed in both PC and BPH, suggesting potential shared molecular pathways between the two conditions. As a fraction of leukocytes may be recruited to the pathological tissues and can migrate back into the circulation/blood, the observed alterations in leukocytes may reflect dynamic changes associated with the PC development, suggesting their potential utility as early markers of prostate cancer development.
良性前列腺增生症（BPH）和前列腺癌（PC）是老年男性中非常常见的疾病。这两种疾病都涉及前列腺内异常的细胞分裂和分化。然而，这两种疾病之间的直接联系仍然存在争议。大量研究表明，炎症是这两种疾病的主要致病因素。另一个与 PC 发展相关的关键因素是 DNA 甲基化和羟甲基化。
通过二维超高效液相色谱-串联质谱法分析了 BPH、PC 和边缘组织以及患者和对照组白细胞中的广泛参数，包括表观遗传 DNA 修饰和 8-氧-7,8-二氢-2'-脱氧鸟苷。在相同的材料中，使用 RT-qPCR 测量了 TETs 和 TDG 基因的表达。此外，还定量了血浆和细胞内（白细胞和前列腺组织）的维生素 C。
与对照样本相比，在 BPH 和 PC 组织以及白细胞中发现了独特的 DNA 修饰和细胞内维生素 C（iVC）模式。大多数改变在白细胞中比在前列腺组织中更为明显。
在 PC 和 BPH 中观察到特征性的甲基化/羟甲基化和 iVC 谱，表明这两种情况之间可能存在共同的分子途径。由于白细胞的一部分可能被募集到病变组织中，并可迁移回循环/血液中，因此白细胞中观察到的改变可能反映与 PC 发展相关的动态变化，提示它们可能作为前列腺癌发展的早期标志物具有潜在的应用价值。
