Pin1 is overexpressed and correlates with poor prognosis in gastric cancer.

Abstract

The prolyl isomerase Pin1, which isomerizes the p-Ser/Thr-Pro peptide bonds and effects conformational and functional changes of the bound proteins, has been identified as a regulator of phosphorylation signaling in several diseases including cancer. The aim of this study is to determine the expression status of Pin1 in gastric cancer, its relationship between clinicopathologic features and patients' outcome. The mRNA levels of Pin1 in human normal and gastric cancer tissues were analyzed using the datasets from the publicly available Oncomine database ( www.oncomine.org ). Pin1 protein levels in human gastric cancer cells and tissues were analyzed by Western blot and immunohistochemistry staining, respectively. The Pin1 protein expression levels and its clinicopathologic correlations were investigated using tumor tissue microarray including 182 cases of human gastric cancer samples with survival information. Pin1 mRNA expression was found to be overexpressed in gastric cancer by using several datasets of Oncomine database analyzing. Pin1 protein expression is higher in 10 gastric cancer cell lines than that in normal gastric epithelial cell line GES-1. Pin1 positive expression was observed in 109 of 182 (59.9 %) gastric cancer samples and in 55 of 182 (30.2 %) normal gastric tissues (P < 0.001). Correlation analysis showed that high expression of Pin1 was significantly associated with pT (P = 0.017), pN (P = 0.043), TNM staging (P = 0.027), Lauren's classification (P < 0.001), as well as shorter overall survival in gastric cancer patients (29 mos vs. 47 mos. P = 0.048). Moreover, Pin1 expression, pT, and differentiation were independent prognostic factors of gastric cancer in Cox regression analysis. Pin1 is overexpressed in gastric cancer and correlates with clinicopathologic features, which might predict poor prognosis of gastric cancer patients.