Wach Sven, Al-Janabi Omar, Weigelt Katrin, Fischer Kersten, Greither Thomas, Marcou Marios, Theil Gerit, Nolte Elke, Holzhausen Hans-Juergen, Stöhr Robert, Huppert Verena, Hartmann Arndt, Fornara Paolo, Wullich Bernd, Taubert Helge
Department of Urology, Universitätsklinikum Erlangen, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Department of Urology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Int J Cancer. 2015 Sep 15;137(6):1406-16. doi: 10.1002/ijc.29505. Epub 2015 Mar 18.
This study aimed to assess the applicability of miR-375 in combination with the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. miR-375 levels by qRT-PCR and suPAR levels by ELISA were evaluated in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Antigen levels of suPAR differed between healthy controls and PCa or BPH patients, whereas miR-375 levels differed between PCa and BPH patients or healthy controls (p < 0.001). Additionally, suPAR levels differed between the Gleason sum groups GS = 7 versus GS > 7, with higher levels in the latter group (p = 0.011), and miR-375 levels were higher in the tumor stage group T3-T4 compared with the T1-T2 group (p = 0.039). A high concentration of suPAR was associated with a poor disease-specific survival (DSS; p = 0.039). The combination of suPAR and miR-375 levels identified a patient group possessing high levels for both parameters. This was associated with a poorer 10-year overall survival (OS) and DSS, with a 6.38-fold increased risk of death and a 7.68-fold increased risk of tumor-related death (p = 0.00026 and p = 0.014; univariate Cox's regression analysis). In a multivariate Cox's regression analysis PCa patients with high levels of suPAR and miR-375 showed a 5.72-fold increased risk of death in OS (p = 0.006). In summary, the differences between the PCa/BPH/healthy control cohorts for either suPAR and miR-375 levels in conjunction with the association of combined high suPAR/miR-375 levels with a poor prognosis suggest a diagnostic and prognostic impact for PCa patients.
本研究旨在评估miR-375与可溶性尿激酶型纤溶酶原激活物受体（suPAR）蛋白联合作为前列腺癌（PCa）患者诊断和/或预后生物标志物的适用性。通过qRT-PCR检测146例PCa患者、35例良性前列腺增生（BPH）患者和18例健康对照者血清样本中的miR-375水平，通过ELISA检测suPAR水平。健康对照者与PCa或BPH患者之间的suPAR抗原水平存在差异，而PCa与BPH患者或健康对照者之间的miR-375水平存在差异（p<0.001）。此外，Gleason评分总和为7组与>7组之间的suPAR水平存在差异，后者水平更高（p=0.011），肿瘤分期为T3-T4组的miR-375水平高于T1-T2组（p=0.039）。高浓度的suPAR与较差的疾病特异性生存率（DSS；p=0.039）相关。suPAR和miR-375水平的联合鉴定出一组两个参数水平均较高的患者。这与较差的10年总生存率（OS）和DSS相关，死亡风险增加6.38倍，肿瘤相关死亡风险增加7.68倍（p=0.00026和p=0.014；单变量Cox回归分析）。在多变量Cox回归分析中，suPAR和miR-375水平高的PCa患者在OS中的死亡风险增加5.72倍（p=0.006）。总之，PCa/BPH/健康对照队列中suPAR和miR-375水平的差异，以及高suPAR/miR-375水平联合与不良预后的关联，提示其对PCa患者具有诊断和预后意义。
