title: Dishevelled segment polarity protein 3 (DVL3): a novel and easily applicable recurrence predictor in localised prostate adenocarcinoma.
abstract: To identify new biomarkers for biochemical recurrence (BCR) of prostate adenocarcinoma.
  
  
  
  Clinical information of 500 patients with prostate adenocarcinoma 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 analysed according to the Gleason grade groups reflecting BCR. The results obtained from the analysis using TCGA dataset were confirmed by immunohistochemistry analyses of a confirmation cohort composed of 395 patients with localised prostate adenocarcinoma.
  
  
  
  TCGA discovery set was subgrouped into lower- and higher-risk groups for recurrence-free survival (RFS) (P < 0.001). Cyclin B1 (CCNB1), dishevelled segment polarity protein 3 (DVL3), paxillin (PXN), RAF1, transferrin, X-ray repair cross complementing 5 (XRCC5) and BIM had lower expression in the lower-risk group than that in the higher-risk group (all, P < 0.05). In TCGA validation set, CCNB1, DVL3, transferrin, XRCC5 and BIM were also differently expressed between the two groups. Immunohistochemically, DVL3 positivity was associated with high prostate-specific antigen (PSA) levels, 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 levels, 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 (hazard ratio 1.80, P = 0.040), and the concordance index (C-index) was 0.805.
  
  
  
  DVL3 and BIM were expressed in patients with a higher risk of BCR. DVL3 may be a novel and easily applicable recurrence predictor of localised prostate adenocarcinoma.
authors.affiliation: Biomedical Knowledge Engineering Laboratory, Seoul National University School of Dentistry and Dental Research Institute, Seoul, Korea.
authors.forename: Pil-Jong
authors.initials: PJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Korea.
authors.forename: Ji Y
authors.initials: JY
authors.lastname: Park
authors.affiliation: Biomedical Knowledge Engineering Laboratory, Seoul National University School of Dentistry and Dental Research Institute, Seoul, Korea.
authors.forename: Hong-Gee
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Yong Mee
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Heounjeong
authors.initials: H
authors.lastname: Go
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism*; D015331:Cohort Studies; D018572:Disease-Free Survival; D000072261:Dishevelled Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000378:metabolism*; D011467:Prostate / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins
keywords: #PCSM; #ProstateCancer; biochemical recurrence; dishevelled segment polarity protein 3; immunohistochemistry; prostate adenocarcinoma; recurrence-free survival