Universitätsklinik für Urologie und Kinderurologie, Otto-von-Guericke-Universität, Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany.
Klinik für Urologie und Kinderurologie, Ruppiner Kliniken, Fehrbelliner Strasse 38, 16816, Neuruppin, Germany.
World J Urol. 2018 Feb;36(2):187-192. doi: 10.1007/s00345-017-2145-y. Epub 2017 Dec 4.
The cytokine system RANKL (receptor activator of NF-κB ligand), its receptor RANK and the antagonist OPG (osteoprotegerin) play a critical role in bone turnover. Our investigation was conducted to describe the gene expression at primary tumour site in prostate cancer patients and correlate the results with Gleason Score and PSA level.
Seventy-one samples were obtained from prostate cancer patients at the time of radical prostatectomy and palliative prostate resection (n = 71). Patients with benign prostate hyperplasia served as controls (n = 60). We performed real-time RT-PCR after microdissection of the samples.
The mRNA expression of RANK was highest in tumour tissue from patients with bone metastases (p < 0.001) as compared to BPH or locally confined tumours, also shown in clinical subgroups distinguished by Gleason Score (< 7 or ≥ 7, p = 0.028) or PSA level (< 10 or ≥ 10 µg/l, p = 0.004). RANKL and OPG mRNA expression was higher in tumour tissue from patients with metastatic compared to local disease. The RANKL/OPG ratio was low in normal prostate tissue and high tumours with bone metastases (p < 0.05). Expression of all three cytokines was high in BPH tissue but did not exceed as much as in the tumour tissue.
We demonstrated that RANK, RANKL and OPG are directly expressed by prostate cancer cells at the primary tumour site and showed a clear correlation with Gleason Score, serum PSA level and advanced disease. In BPH, mRNA expression is also detectable, but RANK expression does not exceed as much as compared to tumour tissue.
细胞因子系统 RANKL（核因子-κB 配体受体激活剂）、其受体 RANK 和拮抗剂 OPG（骨保护素）在骨转换中起着关键作用。我们的研究旨在描述前列腺癌患者原发肿瘤部位的基因表达，并将结果与 Gleason 评分和 PSA 水平相关联。
在根治性前列腺切除术和姑息性前列腺切除术时，从 71 例前列腺癌患者中获取 71 个样本（n=71）。良性前列腺增生患者作为对照（n=60）。我们对样本进行微切割后进行实时 RT-PCR。
与 BPH 或局部局限肿瘤相比，骨转移患者肿瘤组织中 RANK 的 mRNA 表达最高（p<0.001），也在按 Gleason 评分（<7 或≥7，p=0.028）或 PSA 水平（<10 或≥10μg/l，p=0.004）区分的临床亚组中显示。与局部疾病相比，转移性肿瘤组织中 RANKL 和 OPG 的 mRNA 表达更高。正常前列腺组织中的 RANKL/OPG 比值较低，而有骨转移的肿瘤组织中比值较高（p<0.05）。所有三种细胞因子在 BPH 组织中的表达都很高，但不及肿瘤组织高。
我们证明 RANK、RANKL 和 OPG 直接在原发肿瘤部位由前列腺癌细胞表达，并与 Gleason 评分、血清 PSA 水平和晚期疾病有明显的相关性。在 BPH 中，也可检测到 mRNA 表达，但 RANK 表达不及肿瘤组织高。
