作者：杨东杰1,2，王志雄1,2，徐建波1,2，吴晖1,2，李广华1,2，张信华1,2，蔡世荣1,2，陈创奇1,2，王昭1,2，何裕隆1,2,3

单位：1.中山大学附属第一医院 胃肠外科中心，广东 广州 510080； 2.中山大学 胃癌诊治研究中心，广东 广州 510080； 3.中山大学附属第七医院 消化医学中心，广东 广州 510080

Authors:  YANG Dongjie1,2，WANG Zhixiong1,2，XU Jianbo1,2，WU Hui1,2，LI Guanghua1,2，ZHANG Xinhua1,2，CAI Shirong 1,2，CHEN Chuangqi1,2，WANG Zhao1,2，HE Yulong1,2,3

Unit: 1. The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China;  2. Zhongshan University Center for Diagnosis and Treatment of Gastric Cancer, Guangzhou 510080, Guangdong, China;  3. Center for Digestive Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong, China

摘要：

目的  探讨PHLPP2在癌旁正常胃黏膜、胃癌原发灶和淋巴结转移灶中的表达差异。并分析PHLPP2表达水平和胃癌病人临床病例特征和总生存时间的关系。方法  应用免疫组化方法检测PHLPP2在221例胃癌原发灶、30癌旁正常组织和175例淋巴结转移灶中的表达情况,并统计分析了PHLPP2表达与胃癌临床病理特征及其对生存预后的关系。结果  癌旁正常胃黏膜、胃癌原发灶和淋巴结转移灶中的PHLPP2的阳性表达率分别为:70.0%、31.3%和18.3%,组间差异均有统计学意义(31.3% vs. 70.0%, 18.3%vs. 70.0%,31.3%vs. 18.3%, P值均<0.001);并且,PHLPP2的表达与远处转移和TNM分期存在显著相关性;PHLPP2阳性表达的胃癌患者5年生存率为57%,阴性表达胃癌患者5年生存时间仅为35%,差别有统计学意义,P=0.03。多因素生存分析发现PHLPP2是胃癌的独立预后因素(HR 0.56, 95%CI 0.37～0.85, P=0.006)。结论  PHLPP2在胃癌及转移淋巴结中呈低表达, PHLPP2阴性与肿瘤远处转移及更差的预后相关。PHLPP2蛋白有可能成为胃癌预后预测的标志物。

关键词： PHLPP2; 胃癌; 5年生存率

Abstract：

Objective  To detect the expression of PHLPP2 (PH domain leucine-rich repeat protein phosphatase 2) in primary gastric tumors and to explore its impact on the prognosis. Methods Expression of PHLPP2 was assessed by Western Blot and immunohistochemistry method in patients with gastric cancer. Survival analysis according to PHLPP2 expression was calculated. Results  The expression of PHLPP2 protein in primary gastric cancer tissues is downregulated compared with adjacent normal stomach mucosa tissues. The positive rates of PHLPP2 protein in primary gastric cancer tissues and metastatic lymph nodes were significantly lower than in normal stomach mucosa tissues (31.3% vs 70.0%, 18.3% vs 70.0%, both P<0.001). The 5-year overall survival rates of patients with or without PHLPP2 expression were 57% and 35%, respectively (p=0.003). Moreover, PHLPP2 was an independent prognostic factor for OS of gastric cancer patients (HR 0.56, 95%CI 0.37~0.85, P=0.006). Conclusions  Our data suggests that the loss of PHLPP2 expression occured in gastric cancer and is correlated with poor prognosis, which can be a potential prognosis predictor of patients with gastric cancer.

Key Words:  PHLPP2; Gastric Cancer; 5-year Overall Survival