上皮钙黏蛋白和神经钙黏蛋白以及β-连环蛋白在喉鳞状细胞癌中的表达及临床意义

摘要

目的 检测上皮间质转化(Epithelial-mesenchymal transition,EMT)标志物上皮钙黏蛋白(E-cadherin,E-cad)、神经钙黏蛋白(N-cadherin,N-cad)、β-连环蛋白(β-catenin,β-cat)在喉鳞状细胞癌组织中的表达并分析其与临床病理特征及预后的关系.方法 采用免疫组化方法检测76例喉癌组织及其对应的癌旁正常组织中E-cad、N-cad、β-cat蛋白的表达水平,分析其与各临床病理特征之间的关系,再结合临床随访资料,用Kaplan-Meier法绘制生存曲线,Log-rank法比较各组和预后的关系,Cox回归模型分析喉癌预后的独立预测因素.结果 E-cad、N-cad、β-cat在癌和癌旁组织中的表达水平差异均有统计学意义(P＜0.001).喉癌组织中E-cad表达水平与淋巴结转移、临床病理分期、分化程度有关(P＜0.05);N-cad表达水平与临床病理分期、分化程度有关(P＜0.05);β-cat表达水平与淋巴结转移、临床病理分期、分化程度有关(P＜0.05).E-cad与β-cat的表达相关(P =0.001),N-cad与β-Cat的表达相关(P=0.02),而E-cad与N-cad的表达不相关.联合分析E-cad/N-cad:E-cad(+)/N-cad(-)、E-cad(+)/N-cad(+)、E-cad(-)/N-cad(-)、E-cad(-)/N-cad(+),各组的表达水平与临床病理分期及分化程度有关(P＜0.05);同理联合分析E-cad/β-cat示各组的表达水平与淋巴结转移、临床病理分期及分化程度有关(P＜0.01).Log-rank法分析表明,喉癌组织中E-cad、N-cad、β-cat阳性组与阴性组的预后差异有统计学意义(P＜0.05);联合分析表明,E-cad/N-cad,E-cad/β-cat各组的预后差异亦有统计学意义(P＜0.01).Cox回归模型分析表明,临床病理分期、β-cat是喉癌预后的独立预测因素,E-cad、N-cad表达水平不能单独预测疾病的预后.结论 E-cad表达减低,N-cad、β-cat异常表达增高,在喉癌的发生、发展中起到重要的作用,可为评估临床预后提供参考;喉癌的临床病理分期、β-catenin可作为独立预测疾病预后的因子.%Objective To investigate the expression of E-cadherin(E-cad),N-cadherin(N-cad),β-catenin (β-cat),which are the markers of Epithelial-mesenchymal transition and analyze their relationships with the clinicopathological features and the prognosis of the laryngeal squamous cell carcinoma.Methods The expression levels of E-cad,N-cad,β-cat in 76 tumor tissues and their corresponding adjacent normal laryngeal tissues were determined by immunohistochemistry method.Relationships between the proteins' expression and clinicopathological features were analyzed.Survival curves were calculated using the Kaplan-Meier method.Differences in the survival rates were analyzed by the log-rank test among different expression groups.Cox's regression model was used to examine the independent predictor of the prognosis of the laryngeal cancer.Results The expression levels of E-cad,N-cad,β-cat in tumor tissues and adjacent normal tissues were statistically significant (P ＜ 0.001).The expression level of E-cad and β-cat in the laryngeal carcinoma was related to lymph node metastasis,clinical pathological stage and differentiation degree (P ＜ 0.05),while N-cad expression level was associated with clinical stage and differentiation degree (P＜0.05).The expression of E-cad was correlated with the expression of β-cat (P =0.001),and the expression of N-cad was correlated with β-cat (P =0.02),but the expression of E-cad was not correlated with N-cad.There were four subgroups of patterns of E-cad and N-cad expression:E-cad (+)/N-cad (-),E-cad (+) /N-cad (+),E-cad (-) /N-cad (-),E-cad (-) /N-cad (+).The expression level of each group was related to the clinical pathological stage and differentiation degree (P ＜ 0.05).The expression level of E-cad/β-cat was associated with lymph node metastasis,clinical pathological stage and differentiation degree (P ＜ 0.01).Log-rank analysis showed that the prognosis of negative and positive groups was statistically different (P ＜ 0.05),and the combined analysis showed that the prognosis of E-cad/N-cad or E-cad/β-cat group was significantly different (P ＜ 0.01).Cox's regression model analysis showed that the clinical stage and β-cat were independent predictors of the prognosis of laryngeal carcinoma.Conclusions The low expression of E-cad,high abnormal expression of N-cad and β-cat played an important role in the occurrence and development of laryngeal carcinoma.It can provide a reference for evaluating clinical prognosis.The clinical pathological stage and β-cat can be used as independent predictors for the prognosis of laryngeal carcinoma.