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

PLoS One. 2017 Nov 30;12(11):e0189000. doi: 10.1371/journal.pone.0189000. eCollection 2017.

Abstract

Background: 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.

Methods: 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).

Results: 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).

Conclusions: 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.

MeSH terms

  • Aged
  • Cohort Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein Tyrosine Phosphatases / metabolism*

Substances

  • Neoplasm Proteins
  • PTP4A3 protein, human
  • Protein Tyrosine Phosphatases

Grants and funding

Funders are NTNU Norwegian University of Science and Technology, Trondheim, Norway, Kreftforeningen and HelseNord RHF. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.