Abstract
Wnt5a, a member of non-canonical wingless-related MMTV integration site family is a secreted glycoprotein that plays important roles in development and disease. Recent studies have shown that Wnt5a protein levels are up-regulated in prostate cancer, but contrasting reports exist on the role of Wnt5a to predict outcome after radical prostatectomy in patients with localized prostate cancer. Our group has recently shown that preserved high protein expression of Wnt5a in prostate cancer is associated with longer relapse-free time after radical prostatectomy. The present tissue microarray study emphasizes the role of Wnt5a protein expression in a different, well-defined, and independent cohort consisting of 312 prostate cancer patients. Kaplan-Meier curves plotted between Wnt5a expression and time to biochemical recurrence revealed that in low-grade prostate cancer, patients with preserved high-Wnt5a protein levels in their tumor cells have a lower risk of recurrence after radical prostatectomy compared to patients with low-Wnt5a protein expression. When Wnt5a protein expression was added to a Cox regression multivariate analysis, both Wnt5a protein expression and surgical margin status independently predict biochemical free survival. Herein we confirm Wnt5a positivity as a prognostic factor and show that preserved overexpression of Wnt5a protein is associated with increased time to biochemical recurrence in localized low-grade prostate cancer patients after radical prostatectomy. Our results emphasize that Wnt5a can be used as a predictive biomarker, and favoring the view of Wnt5a as a future therapeutic target in prostate cancer patients with tumor cells displaying low expression of Wnt5a.