title: Elevated level of Wnt5a protein in localized prostate cancer tissue is associated with better outcome.
abstract: BACKGROUND
  Wnt5a is a non-canonical secreted glycoprotein of the Wnt family that plays an important role in cancer development and progression. Previous studies report that Wnt5a is upregulated in prostate cancer and suggested that Wnt5a affects migration and invasion of prostate tumor cell. This study aimed to evaluate the prognostic value of Wnt5a protein expression in prostate cancer tissue and its potential to predict outcome after radical prostatectomy in patients with localized prostate cancer.
  
  
  RESULTS
  Immunohistochemical analysis of a tissue microarray containing prostate specimens of 503 patients with localized prostate cancer showed significantly higher Wnt5a protein expression in cancer compared to benign cores from the same patients (p<0.0001). Patients with high expression of Wnt5a protein had significantly better outcome in terms of time to biochemical recurrence compared to patients with low expression levels (p = 0.001, 95%CI 1.361-3.570, Hazard's ratio 2.204). A combination of high Wnt5a expression with low levels of Ki-67 or androgen receptor expression had even better outcome compared to all other groups. Furthermore, we found that Wnt5a expression significantly correlated with VEGF and with Ki-67 and androgen receptor expression, although not highly significant. In vitro, we demonstrated that recombinant Wnt5a decreased invasion of 22Rv1 and DU145 cells and that siRNA knockdown of endogenous Wnt5a protein led to increased invasion of 22Rv1 and LNCaP cells.
  
  
  CONCLUSIONS
  We demonstrate that preserved overexpression of Wnt5a protein in patients with localized prostate cancer predicts a favorable outcome after surgery. This finding together with our in vitro data demonstrating the ability of Wnt5a to impair the invasive properties of prostate cancer cells, suggests a tumor suppressing effect of Wnt5a in localized prostate cancer. These results indicate that Wnt5a can be used as a predictive marker and that it also is a plausible therapeutic target for treatment of localized prostate cancer.
authors: Division of Urological Cancers, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
authors: Azharuddin Sajid
authors: AS
authors: Syed Khaja
authors: Leszek
authors: L
authors: Helczynski
authors: Anders
authors: A
authors: Edsjö
authors: Roy
authors: R
authors: Ehrnström
authors: Anna
authors: A
authors: Lindgren
authors: David
authors: D
authors: Ulmert
authors: Tommy
authors: T
authors: Andersson
authors: Anders
authors: A
authors: Bjartell
mesh_terms: D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; D011944:Receptors, Androgen; D042461:Vascular Endothelial Growth Factor A; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein