Department of Radiotherapy, Multidisciplinary Hospital in Gorzów Wielkopolski, Gorzów Wielkopolski, Poland.
Department of Urology, Multidisciplinary Hospital in Gorzów Wielkopolski, Gorzów Wielkopolski, Poland.
Med Sci Monit. 2020 Dec 16;26:e925860. doi: 10.12659/MSM.925860.
BACKGROUND Biomarkers predicting the efficacy of treatment for locally limited prostate cancer are greatly needed. This knowledge could improve the classification of patients for different methods of treatment and enable better recognition of groups with higher risk of biological recurrence. We prospectively assessed serial blood levels of apoptotic biomarkers and correlated them with response to treatment and clinical factors. MATERIAL AND METHODS Blood was collected from 25 patients with prostate cancer before and after surgery, 16 healthy volunteers with benign prostatic hyperplasia (BPH), and 14 patients with metastasized disease. Immunoenzymatic methods were used to determine circulating apoptotic and inflammatory mediators, including tumor necrosis factor alpha (TNF-alpha), type I receptor (TNFRI), and type II receptor (TNFRII); FAS ligand (FasL); TNF-related apoptosis-inducing ligand (TRIAL); caspase 8 (Cas8); caspase 9 (Cas9); DNA methylation (metDNA); P-selectin; and high-sensitivity C-reactive protein. The total circulating fragments of cell-free DNA (cfDNA) were measured directly in serum. RESULTS Peripheral serum prostate-specific antigen increased rapidly together with cfDNA. A negative correlation was noted between tumor volume and TNFRI and TNFRII. Postsurgery P-selectin level was decreased, and metDNA and TNFRII levels were increased. Three comparisons were made between patient groups: surgical vs. BPH; surgical vs. palliative; and palliative vs. BPH. TNFRI, TNFRII, metDNA, P-selectin, Cas8, and FasL were shown to have significant roles. CONCLUSIONS The study indicated significant roles for cfDNA, both TNF receptors, metDNA, and P-selectin as serum biomarkers in patients with prostate cancer.
目前非常需要能够预测局部局限性前列腺癌治疗效果的生物标志物。这方面的知识可以改善患者的分类，为不同的治疗方法提供依据，并更好地识别出生物学复发风险较高的群体。我们前瞻性评估了凋亡生物标志物的血清水平，并将其与治疗反应和临床因素相关联。
采集了 25 例前列腺癌患者手术前后、16 例良性前列腺增生（BPH）患者和 14 例转移性疾病患者的血液。采用免疫酶法测定循环凋亡和炎症介质，包括肿瘤坏死因子-α（TNF-α）、I 型受体（TNFRI）和 II 型受体（TNFRII）、FAS 配体（FasL）、肿瘤坏死因子相关凋亡诱导配体（TRAIL）、半胱天冬酶 8（Cas8）、半胱天冬酶 9（Cas9）、DNA 甲基化（metDNA）、P-选择素和高敏 C 反应蛋白。直接在血清中测量总循环游离 DNA（cfDNA）片段。
外周血前列腺特异性抗原（PSA）与 cfDNA 一起迅速升高。肿瘤体积与 TNFRI 和 TNFRII 呈负相关。手术后 P-选择素水平下降，metDNA 和 TNFRII 水平升高。将患者分为三组进行比较：手术组与 BPH 组；手术组与姑息治疗组；姑息治疗组与 BPH 组。结果显示 TNFRI、TNFRII、metDNA、P-选择素、Cas8 和 FasL 具有显著作用。
本研究表明 cfDNA、两种 TNF 受体、metDNA 和 P-选择素在前列腺癌患者中具有重要的血清标志物作用。
