Objective To detect the expressions of enhancer of zeste homology 2 (EZH2) and signal transducer and activator of transcription 3 (STAT3) in gastric cancer tissues,and analyze the relationship between their expressions and clinicopathological factors and prognosis of patients.Methods The clinical data of 67 patients with gastric cancer who were admitted to the People's Hospital of Peking University from May 1999 to April 2000 were retrospectively analyzed.Gastric cancer tissues and adjacent normal tissues were harvested and fixed in 4％ formaldehyde,and then to make the tissue chips.The protein expressions of EZH2 and STAT3 were detected by immunohistochemical staining,and the relationship between the expressions of EZH2 and STAT3 and the prognosis of patients was analyzed.The correlation between the protein expressions of EZH2 and STAT3 in the gastric and colorectal tissues and the clinicopathological parameters was analyzed using the paired chi-square test.The survival curve was drawn by Kaplan-Meier method,and the survival rate was analyzed by using the Logrank test.The relationship between the clinicopathological factors and the prognosis of patients was analyzed using the COX proportional hazard model.Results The positive protein expression rates of EZH2 and STAT3 in the gastric cancer tissues were 73.1％ (49/67) and 67.2％ (45/67),which were significantly higher than 32.8％ (22/67) and 37.3％ (25/67) in the adjacent normal tissues (x2=21.839,11.964,P ＜0.05).The protein expression of STAT3 was correlated with the age,TNM staging,lymph node metastatic status (x2=5.475,9.998,5.475,P ＜ 0.05).The protein expression of EZH2 was correlated with TNM staging and lymph node metastatic status (x2=11.573,5.902,P ＜ 0.05).The co-expression rate of EZH2 and STAT3 proteins was 73.1％ (49/67),EZH2 and STAT3 had the common expression trend (r =0.397,P ＜ 0.05).The co-expression rate of EZH2 and STAT3 was increased as the increase of TNM stages,and the co-expression of EZH2 and STAT3 in the gastric cancer tissue was correlated with the TNM stages (x2 =6.997,P ＜ 0.05).The 5-year survival rate of patients with low protein expression of EZH2 was significantly higher than those with high protein expression of EZH2 (x2=7.386,P ＜ 0.05).The 5-year survival rate of patients with low proteins expression of STAT3 was significantly higher than those with high proteins expression of STAT3 (x2=12.253,P ＜ 0.05).The 5-year survival rate of patients with low co-expression of EZH2 and STAT3 protein was significantly higher than those with high co-expression of EZH2 and STAT3 proteins (x2 =8.765,P ＜ 0.05).The results of univariate analysis showed that age,TNM staging,EZH2 and STAT3 expression,lymph node metastasis and distal metastasis were the factors influencing the survival of patients with gastric cancer (RR =2.136,3.452,3.179,8.341,11.773,6.873,P ＜0.05).The results of multivariate analysis showed that TNM staging and STAT3 expression were independent factors influencing the prognosis of patients with gastric cancer (RR =2.453,7.535,P ＜ 0.05).Conclusions There is significant correlation between EZH2 and STAT3 protein expressions in gastric cancer tissues,and co-expression of EZH2 and STAT3 is associated with the TNM staging and the prognosis of the patients with gastric cancer.%目的 检测胃癌组织标本中果蝇zeste基因增强子2(EZH2)和信号转导与转录激活子3(STAT3)的表达情况,并分析其与临床病理学特征以及患者预后关系.方法 回顾性分析1999年5月至2000年4月北京大学人民医院收治的67例胃癌患者的临床资料.连续收集患者手术切除的胃癌组织及癌旁组织(距肿瘤边缘＞5 cm),用4％甲醛固定,常规石蜡包埋后,制作组织芯片,通过免疫组织化学染色法检测组织中EZH2和STAT3的表达情况,并分析其与临床病理学特征以及患者预后关系.胃癌组织中EZH2、STAT3的蛋白表达水平与临床病理指标之间的关系用配对x2检验,Kaplan-Meier法绘制胃癌患者的生存曲线,Log-rank检验生存率,COX比例风险模型分析胃癌各临床病理指标与预后之间的关系.结果 胃癌组织中EZH2和STAT3蛋白的高表达率分别为73.1％ (49/67)和67.2％(45/67),显著高于癌旁组织中的32.8％ (22/67)和37.3％(25/67),两者比较,差异有统计学意义(x2=21.839,11.964,P＜0.05).EZH2蛋白表达水平与TNM分期、有无淋巴结转移相关(x2=11.573,5.902,P＜0.05).STAT3蛋白表达水平与年龄、TNM分期、有无淋巴结转移相关(x2=5.475,9.998,5.475,P＜0.05)；EZH2和STAT3蛋白共同表达率(高表达和低表达合计49例)为73.1％(49/67),EZH2和STAT3蛋白表达呈正相关(r=0.397,P＜ 0.05).EZH2和STAT3蛋白共同高表达率随TNM分期的增高而增高,EZH2和STAT3蛋白在胃癌组织中的共同表达与临床TNM分期有关(x2=6.997,P＜0.05).EZH2蛋白低表达胃癌患者的5年生存率显著高于EZH2蛋白高表达的胃癌患者(x2=7.386,P＜0.05).STAT3蛋白低表达胃癌患者5年生存率显著高于STAT3蛋白高表达的胃癌患者(x2=12.253,P＜0.05).EZH2和STAT3蛋白共同低表达的胃癌患者5年生存率显著高于EZH2和STAT3蛋白共同高表达的胃癌患者(x2=8.765,P＜0.05).单因素分析结果显示:年龄、TNM分期、EZH2表达、STAT3表达、淋巴结转移和远处转移是影响胃癌患者生存的危险因素(RR=2.136,3.452,3.179,8.341,11.773,6.873,P＜0.05).多因素分析结果显示:TNM分期、STAT3表达水平是影响胃癌预后的独立危险因素(RR=2.453,7.535,P＜0.05).结论 胃癌中EZH2及STAT3表达有显著相关性；其联合表达模式可能是判断胃癌TNM分期及患者预后的肿瘤分子标志物.
展开▼
