Hu Chunhui, Chen Beibei, Zhou Yibin, Shan Yuxi
Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 China.
Department of Intensive Care Unit, Huai'an First People's Hospital, Huai'an, 223300 Jiangsu China.
Cancer Cell Int. 2017 Apr 11;17:45. doi: 10.1186/s12935-017-0411-0. eCollection 2017.
Ras-related protein 25 (Rab25) functions either as an oncogene or a tumor suppressor with a cancer type-dependent manner. We aimed to investigate clinical significance of Rab25 in prostate cancer (PCa).
Quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry were respectively performed to detect Rab25 mRNA and protein expression in PCa and adjacent non-cancerous prostate tissues. Receiver-operating characteristic curve analysis was used to evaluate predictive diagnostic value of Rab25. Associations of Rab25 expression with various clinicopathological characteristics and biochemical recurrence-free survival of PCa patients were statistically evaluated. In vitro, PCa cell proliferation was assessed by CCK-8 assay, and the cell migration and invasion activities were evaluated by Transwell assay, following the transfection of Rab25 small interfering RNA.
Ras-related protein 25 mRNA and protein expression in PCa tissues were both significantly higher than adjacent non-cancerous prostate tissues (both P < 0.001). The area under the curve of Rab25 immunoreactive score (IRS) was 0.896 (P < 0.001) with 74.0% sensitivity and 95.0% specificity. High Rab25 IRS was significantly associated with high Gleason score (P = 0.02) and distant metastasis (P = 0.01). PCa patients with high Rab25 IRS had shorter overall and biochemical recurrence-free survivals than those with low Rab25 IRS (both P < 0.001). Cox regression analysis identified Rab25 as an independent biomarker for both overall and biochemical recurrence-free survivals of PCa patients. By exploring its activities in vitro, Rab25 downregulation was found to inhibit PCa cell proliferation, migration and invasion.
High expression of Rab25 may contribute to malignant progression and biochemical recurrence of PCa patients after radical prostatectomy.
Ras相关蛋白25（Rab25）在不同癌症类型中发挥癌基因或抑癌基因的作用。我们旨在研究Rab25在前列腺癌（PCa）中的临床意义。
分别采用定量实时聚合酶链反应、蛋白质免疫印迹法和免疫组织化学法检测PCa组织及相邻非癌前列腺组织中Rab25 mRNA和蛋白表达。采用受试者工作特征曲线分析评估Rab25的预测诊断价值。统计学评估Rab25表达与PCa患者各种临床病理特征及无生化复发生存期的相关性。在体外，转染Rab25小干扰RNA后，通过CCK-8法评估PCa细胞增殖，通过Transwell法评估细胞迁移和侵袭活性。
PCa组织中Rab25 mRNA和蛋白表达均显著高于相邻非癌前列腺组织（均P < 0.001）。Rab25免疫反应评分（IRS）的曲线下面积为0.896（P < 0.001），敏感性为74.0%，特异性为95.0%。高Rab25 IRS与高Gleason评分（P = 0.02）和远处转移（P = 0.01）显著相关。高Rab25 IRS的PCa患者总生存期和无生化复发生存期均短于低Rab25 IRS的患者（均P < 0.001）。Cox回归分析确定Rab25是PCa患者总生存期和无生化复发生存期的独立生物标志物。通过体外研究其活性，发现Rab25下调可抑制PCa细胞增殖、迁移和侵袭。
Rab25高表达可能促进前列腺癌根治术后患者的恶性进展和生化复发。
