Expression of phosphatase of regenerating liver (PRL)-3, is independently associated with biochemical failure, clinical failure and death in prostate cancer.

Abstract

Prostate cancer (PC) stratification needs new prognostic tools to reduce overtreatment. Phosphatase of regenerating liver (PRL-3) is a phosphatase found at high levels in several cancer types, where its expression is associated with survival. A recent PC cell line study has shown it to be involved in PC growth and migration.We used a monoclonal antibody to evaluate the expression of PRL-3 in PC tissue of patients in an unselected cohort of 535 prostatectomy patients. We analyzed associations between PRL-3 expression and biochemical failure-free survival (BFFS), clinical failure-free survival (CFFS) and PC death-free survival (PCDFS).Cytoplasmic PRL-3 staining in tumor cells was significantly correlated to expression of molecules in the VEGFR-axis, but not to the clinicopathological variables. High PRL-3 was not significantly associated with survival in the univariate analysis for BFFS (p = 0.131), but significantly associated with CFFS (p = 0.044) and PCDFS (p = 0.041). In multivariate analysis for the various end points, PRL-3 came out as an independent and significant indicator of poor survival for BFFS (HR = 1.53, CI95% 1.10-2.13, p = 0.012), CFFS (HR = 2.41, CI95% 1.17-4.98, p = 0.017) and PCDFS (HR = 3.99, CI95% 1.21-13.1, p = 0.023).PRL-3 is independently associated with all PC endpoints in this study. Since high PRL-3 expression also correlates with poor prognosis in other cancers and functional studies in PC support these findings, PRL-3 emerges as a potential treatment target in PC.