Wnt/β-catenin通路关键分子在NK/T细胞淋巴瘤组织中的表达及其临床意义

Expressions of key molecules of Wnt/β-catenin signal pathway in NK/T-cell lymphoma tissue and their significances

目的:研究Wnt/β-catenin通路的关键分子β-catenin、c-myc和cyclinD1在NK/T细胞淋巴瘤(NKTCL)组织中的表达,阐明其与NKTCL患者临床特征的关系。方法:采用Real-time PCR法检测人NKTCL细胞株(SNK-6和YTS)及人正常NK细胞中Wnt/β-catenin信号通路相关基因β-catenin、c-myc和cyclinD1 mRNA的表达水平;采用免疫组织化学SP法检测NKTCL组织和反应性增生的淋巴组织中β-catenin、c-myc蛋白的表达阳性率,并分析蛋白表达与患者临床特征的关系;分析NKTCL患者中β-catenin和c-myc蛋白表达的相关性;Kaplan-Meier法分析β-catenin表达与NKTCL患者中位生存期的关系。结果:细胞株SNK-6和YTS中β-catenin、c-myc和cyclinD1mRNA的表达阳性率明显高于正常NK细胞(P<0.05);NKTCL组织中β-catenin和c-myc蛋白表达阳性率(24%和56%)明显高于淋巴结反应性增生组织(0%和25%)(P<0.05);β-catenin表达与Ann Arbor分期有关联(P<0.05),c-myc表达与Ann Arbor分期和Ki-67水平有关联(P<0.05),NKTCL患者中β-catenin和c-myc表达呈正相关关系(r=0.770,P<0.05);β-catenin阳性表达患者中位生存期低于β-catenin阴性表达患者(P<0.05)。结论:Wnt/β-catenin信号通路中关键分子β-catenin、c-myc、cyclinD1在NKTCL组织中高表达,并且其表达水平与NKTCL患者临床分期有关联。

Objective To investigate the expressions of the key moleculesβ-catenin,c-myc,and cyclinD1 of the Wnt/β-catenin signal pathway in the NK/T-cell lymphoma（NKTCL）tissue,and to clarify their relationships with the clinicopathological features of the NKTCL patients.Methods Real-time PCR method was used to detect the expression levels ofβ-catenin,c-myc,and cyclinD1 mRNA in human NKTCL cell lines（SNK-6and YTS）and normal NK cells;the positive expression rates ofβ-catenin and c-myc proteins in the NKTCL tissue and reactive hyperplasia of lymph node tissue were detected by immunohistochemistry SP method;the correlations among the expressions ofβ-catenin and c-myc proteins and the clinicopathological features of the NKTCL patients were analyzed;correlation analysis was used to analyze the relationship between the expressions ofβ-catenin and c-myc proteins of the NKTCL patients;Kaplan-Meier method was used to analyze the relationship between the expression ofβ-catenin and overall survival rate of the NKTCL patients.Results The positive expression rates ofβ-catenin,c-myc,and cyclinD1 mRNA in the SNK-6cell line and YTS cell line were significantly higher than those in the normal NK cells（P〈0.05）;the expressionβ-catenin and c-myc proteins in NKTCL tissue（24% and 56%）were higher than those in reactive hyperplasia of lymph node tissue（0and 25%）（P〈0.05）;the expression ofβ-catenin was correlated with Ann Arbor stage（P〈0.05）,and the expression of c-myc was correlated with Ann Arbor stage and Ki-67（P〈0.05）;there were positive correlations between the expression ofβ-catenin and the expression of c-myc in the NKTCL patients（r=0.770,P〈0.05）;the patients withβ-catenin positive expression had a shorter overall survival time than the patients with negative expression（P〈0.05）.Conclusion The key moleculesβ-catenin,c-myc,and cyclinD1 of the Wnt/β-catenin signal pathway are highly expressed in the human NKTCL tissue,and they show positive correlations with Ann Arbor stage of the NKTCL patients.