Effect of upregulation of DD3 on early detection and prognosis in prostate cancer.

Background: Expression of prostate cancer antigen 3 (PCA3 OR DD3) in the blood has been reported to be significantly higher in prostate cancer (PCa) than in benign prostate hyperplasia (BPH). To confirm whether DD3 expression is significantly different between PCa and BPH tissues, DD3 expression was tested in the blood both preoperatively and postoperatively and in the paired tissues of PCa patients. Methods: Expression levels of DD3 mRNA in the blood of patients who did not undergo surgery (PCa, n=102; BPH, n=53), those underwent surgery (preoperative, n=35; postoperative, n=35), and in PCa tissue specimens (tumor, n=41; adjacent normal, n=21) were determined by real-time quantitative PCR. Sensitivity and specificity for DD3 in PCa patients were validated by receiver operating characteristic (ROC) curve analysis. Results: Our data suggest that expression level of DD3 in blood samples was significantly higher in PCa patients than in BPH patients (P=0.005). Expression of DD3 mRNA was also significantly elevated in PCa tissues compared with adjacent normal tissues (P=0.013). The increase in DD3 expression in PCa patients was further validated using a dataset from The Cancer Genome Atlas (n=549). Postoperative DD3 expression decreased following surgical intervention (P<0.001). Moreover, low DD3 expression was associated with improved overall survival (OS). Using gene set enrichment analysis, DD3 expression was correlated with specific PCa target genes including carcinogenesis-related and cancer proliferation-related genes. Conclusions: This study demonstrated that expression of DD3 was upregulated in blood and PCa tumor tissues and was associated with prognosis. The oncogenic role of DD3 was further validated in the TCGA database, indicating that DD3 is a potential therapeutic target for PCa. Furthermore, this study suggests that DD3 expression could be considered as a prognostic biomarker for PCa.