Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma
Menée sur des échantillons tumoraux prélevés sur 196 patients atteints d'un cancer de l'estomac et 21 patients présentant des métastases hépatiques, puis in vitro, cette étude évalue l'intérêt de mesurer l'expression de la protéine PRL-3 pour le pronostic de la maladie
BACKGROUND:PRL-3 is a member of phosphatases of regenerating liver family, characterized by phosphatase active domain and C-terminal prenylation motif. Overexpression of PRL-3 has been implicated in multiple cancers. Here we examined the clinical significance of PRL-3 in gastric cancer together with its metastatic biological functions utilizing different structural mutants.
METHODS:PRL-3 expression was analyzed immunohistochemically in 196 gastric cancer patients and 21 cases of liver metastasis. A series of wild type PRL-3 or its mutant plasmids were expressed in BGC823 cells to investigate the relationship between its catalytic activity, cellular localization and metastatic potential in vitro.
RESULTS:Positive staining of PRL-3 was observed in 19.4% (38/196) gastric cancer tissues compared with 76.2% (16/21) in liver metastasis. Statistical analysis revealed that PRL-3 expression correlated with lymph node metastasis and vascular invasion (P < 0.05). Patients with high PRL-3 expression showed poorer 5-year overall survival (P = 0.011). Wild type PRL-3 expressing cells resulted in enhanced migration and invasion ability, which were greatly crippled in form of PRL-3(C104S) or PRL-3(DeltaCAAX) mutants accompanied with its alteration in subcellular localization.
CONCLUSIONS:Metastasis associated protein PRL-3 may serve as a potential prognostic biomarker in human gastric cancer. Both the phosphatase catalytic activity and cellular localization are critical for its function.
Journal of Translational Medicine , article en libre accès, 2012