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

Abstract

BackgroundProstate 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.MethodsWe 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).ResultsCytoplasmic 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).ConclusionsPRL-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.

Physiological and oncogenic roles of the PRL phosphatases

“…Similar to the cancers described above, upregulated PRL‐3 in tumors has been found in cervix , kidney , glioma , bladder , melanoma , lung , and prostate cancers. As for PRL‐1 and ‐2, using microarray analysis, mRNA levels were shown to be upregulated in pancreatic tumor samples compared with those of normal pancreas .…”

“…However, one study indicated that PRL-3 expression has no clinical role in ovarian carcinoma, whereas surprisingly PRL-1 and PRL-2 expression is associated with longer survival [113]. Similar to the cancers described above, upregulated PRL-3 in tumors has been found in cervix [114], kidney [115,116], glioma [117,118], bladder [119], melanoma [120], lung [121], and prostate [122][123][124] cancers. As for PRL-1 and -2, using microarray analysis, mRNA levels were shown to be upregulated in pancreatic tumor samples compared with those of normal pancreas [125].…”

Correlation of PRL3 expression with colorectal cancer progression

“…7 Various studies have reported upregulation of PRL3 in CRC. [9][10][11] PRL3 has also been found to be overexpressed in many other human cancer types such as prostate cancer, 12,13 gastric cancer, 14,15 ovarian cancer, 16 and chronic myeloid leukemia. 17 PRL3 promotes cell survival and epithelial to mesenchymal transition (EMT) by acting upstream of phosphatidylinositol-3 kinase (PI3K)/serine threonine protein kinase Akt signaling.…”