Shi Min, Chen Lingxiang, Ji Jun, Cai Qu, Yu Yingyan, Liu Bingya, Zhu Zhenggang, Zhang Jun
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China.
Cell Biochem Biophys. 2015 Mar;71(2):857-64. doi: 10.1007/s12013-014-0274-0.
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.
脯氨酰异构酶Pin1可使p - Ser/Thr - Pro肽键发生异构化，并影响所结合蛋白质的构象和功能变化，已被确定为包括癌症在内的多种疾病中磷酸化信号传导的调节因子。本研究的目的是确定Pin1在胃癌中的表达状态、其与临床病理特征及患者预后的关系。利用公开可用的Oncomine数据库（www.oncomine.org）中的数据集，分析了人正常组织和胃癌组织中Pin1的mRNA水平。分别通过蛋白质印迹法和免疫组织化学染色分析了人胃癌细胞和组织中Pin1蛋白的水平。使用包含182例有生存信息的人胃癌样本的肿瘤组织芯片，研究了Pin1蛋白表达水平及其与临床病理的相关性。通过分析Oncomine数据库的多个数据集发现，Pin1 mRNA表达在胃癌中过表达。10种胃癌细胞系中Pin1蛋白表达高于正常胃上皮细胞系GES - 1。在182例胃癌样本中有109例（59.9%）观察到Pin1阳性表达，在182例正常胃组织中有55例（30.2%）观察到Pin1阳性表达（P < 0.001）。相关性分析表明，Pin1的高表达与pT（P = 0.017）、pN（P = 0.043）TNM分期（P = 0.027）、Lauren分类（P < 0.001）显著相关，并且与胃癌患者较短的总生存期相关（29个月对47个月，P = 0.048）。此外，在Cox回归分析中，Pin1表达、pT和分化是胃癌的独立预后因素。Pin1在胃癌中过表达，并与临床病理特征相关，这可能预示着胃癌患者预后不良。
