Abstract
BackgroundRas-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).MethodsQuantitative 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.ResultsRas-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.ConclusionsHigh expression of Rab25 may contribute to malignant progression and biochemical recurrence of PCa patients after radical prostatectomy.
Highlights
Ras-related protein 25 (Rab25) functions either as an oncogene or a tumor suppressor with a cancer type-dependent manner
Overexpression of Rab25 mRNA and protein in human prostate cancer (PCa) tissues and cells Expression levels of Rab25 mRNA were both significantly higher in PCa tissues and LNCaP cells than those in adjacent non-cancerous prostate tissues and PrEC cells, which was consistent with the data on Rab25 protein obtained from Western blot analysis
The moderately or strongly positive immunostainings of Rab25 protein were observed in the cytoplasm of cancer cells in PCa tissues, while there was only weak or negative immunostainings of Rab25 protein shown in adjacent non-cancerous prostate tissues (Fig. 2a)
Summary
Ras-related protein 25 (Rab25) functions either as an oncogene or a tumor suppressor with a cancer type-dependent manner. Rab is frequently amplified in head and neck tumors [8], gastric cancer [9], ovarian cancer [10], cervical cancer [11], bladder cancer [12] and renal cancer [13], but is downregulated in esophageal cancer [14], breast cancer [15] and colorectal cancer [16]. It acts either as an oncogene or a tumor suppressor with a cancer-specific manner
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