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AIM:To investigate the prognostic significance of phosphatase regenerating liver 3(PRL-3)protein expression in gastric cancer.METHODS:PRL-3 expression in paraffin-embedded tumor specimens from 293 patients with gastric cancer was studied retrospectively by immunohistochemistry.Monoclonal antibody specifically against PRL-3,3B6,was obtained with hybridoma technique.RESULTS:Positive PRL-3 expression was detected in 43.3%(127 of 293)of gastric cancer cases.High expression of PRL-3 was positively correlated with tumor size,depth of invasion,vascular/lymphatic invasion,lymph node metastasis,high TNM stage and tumor recurrence.Patients with positive PRL-3 expression had a significantly lower 5-year survival rate than those with negative expression(28.3%vs 51.9%,P<0.0001).Patients who received curative surgery,and with positive PRL-3 expression had a significant shorter overall survival and disease-free disadvantage over patients with negative expression(hazard ratio of 16.7 and 16.6,respectively;P<0.0001 for both).Multivariate analysis revealed that PRL-3 expression was an independent prognostic indicator for overall and disease-free survival of gastric cancer patients,particularly for survival in TNM stageⅢpatients.CONCLUSION:PRL-3 expression is a new independent prognostic indicator to predict the potential of recurrence and survival in patients with gastric cancer at the time of tumor resection.