Dishevelled segment polarity protein 3 (DVL3): a novel and easily applicable recurrence predictor in localized prostate adenocarcinoma

Objective To identify new biomarkers for the biochemical recurrence (BCR) of prostate adenocarcinoma. Patients and Methods Clinical information of 500 prostate adenocarcinoma patients and their 152 RNA-sequencing and protein-array data from The Cancer Genome Atlas (TCGA) were separated into a discovery-set and a validation-set. Each dataset was analyzed according to the Gleason grade groups reflecting BCR. The results obtained from the analysis using TCGA dataset were confirmed by immunohistochemistry analyses of the confirmation cohort composed of 395 localized prostate adenocarcinoma patients. Results TCGA discovery set was subgrouped into lower-risk and higher-risk groups for recurrence-free survival (RFS) (P<0.001). CCNB1, DVL3, PXN, RAF1, Transferrin, XRCC5 and Bim exhibited lower expression in the lower-risk group compared with that of the higher-risk group (all, P<0.05). In TCGA validation set, CCNB1, DVL3, Transferrin, XRCC5 and Bim were also differently expressed between two groups. DVL3-positivity was associated with high prostate specific antigen (PSA), resection margin involvement, and BCR (all, P<0.05). A high Gleason score indicated a marginal relationship (P=0.055). Bim-positivity was related to high PSA, lymphovascular invasion and BCR (all, P<0.05). Both DVL3-positivity (P=0.010) and Bim-positivity (P=0.024) were associated with shorter RFS, but statistical significance was lost when the multivariate Cox regression model included all patients. In the lower-risk group, the multivariate Cox model confirmed that DVL3 was an independent predictor for poor RFS (HR=1.80, P=0.040), and the C-index was 0.805. Conclusions DVL3 and Bim were expressed in the group with higher-risk for BCR. DVL3 may be a novel and easily applicable recurrence predictor of localized prostate adenocarcinoma. This article is protected by copyright. All rights reserved.