目的:探讨丝裂原活化蛋白激酶4(MKK4)、生存素(Survivin)基因在喉鳞状细胞癌组织中的表达及其意义.方法:选择82例喉癌患为研究对象,取手术切除的喉癌组织及癌旁正常黏膜组织,采用逆转录聚合酶链反应(RT-PCR)法、免疫组织化学法检测MKK4、Survivin基因表达,分析其与临床病理特征的关系,随访记录喉癌患者5年生存率,并用Cox回归模型对喉癌患者预后因素进行分析.结果:喉癌组织中MKK4 mRNA表达较癌旁组织下降,喉癌组织中Survivin mRNA表达较癌旁组织升高(均P<0.05).癌旁组织和喉癌组织MKK4蛋白阳性表达率分别为 71.95%(59/82)和 40.24%(33/82),Survivin 蛋白阳性表达率分别为 23.17%(19/82)和 71.95%(59/82)(x2=16.737,x2=39.117,均P<0.01).不同肿瘤分化程度、TNM分期及有无淋巴结转移患者MKK4、Survivin蛋白阳性表达比较,差异有统计学意义(均P<0.05).喉癌组织中MKK4和Survivin表达呈负相关(r=-0.403,P<0.05).MKK4阳性患者5年生存率81.82%(27/33)高于阴性患者65.31%(32/49),Survivin阳性患者5年生存率62.71%(37/59)低于阴性患者82.61%(19/23),影响喉癌患者预后的因素为TNM分期和MKK4、Survivin表达(均P<0.05).结论:喉癌组织中MKK4表达下调,Survivin表达上调,两者可能是潜在的预后标记物以及治疗靶点.
Objective:To investigate the expression and significance of mitogen-activated protein kinase kinase 4(MKK4)and Survivin in laryngeal squamous cell carcinoma.Methods:Eighty-two cases of laryngeal cancer were se-lected as the research objects.The expression levels of MKK4 and Survivin in laryngeal cancer tissues and adjacent normal mucosa tissues were detected by RT-PCR and immunohistochemistry,and the relationship between MKK4,Survivin and clinicopathological characteristics was analyzed.The patients were followed up for 5 years,and the sur-vival rate of patients with laryngeal cancer was recorded.Cox proportional hazards regression model was used to ana-lyze the prognostic factors of patients with laryngeal cancer.Results:The expression of MKK4 mRNA in laryngeal carcinoma tissues was lower than that in paracancer tissues,while Survivin mRNA expression was higher in laryngeal carcinoma tissues(all P<0.05).The positive expression rates of MKK4 protein in adjacent tissues and laryngeal cancer tissues were 71.95%(59/82)and 40.24%(33/82),and the positive expression rates of Survivin protein were 23.17%(19/82)and 71.95%(59/82),respectively(x2=16.737,39.117,all P<0.01).There were significant differ-ences in the expression of MKK4 and Survivin in tumor differentiation,TNM stage,and lymph node metastasis in la-ryngeal carcinoma tissues(all P<0.05).There was a negative correlation between MKK4 and Survivin expression in laryngeal carcinoma tissues(r=-0.403,P<0.05).The 5-year survival rate of MKK4-positive patients was 81.82%(27/33),higher than 65.31%(32/49)of negative patients(P<0.05).The 5-year survival rate of survivin-positive patients was 62.71%(37/59),lower than 82.61%(19/23)of negative patients(P<0.05).TNM stage,MKK4 and Survivin were independent prognostic factors in patients with laryngeal cancer(all P<0.05).Conclusion:MKK4 ex-pression is down-regulated and Survivin expression is up-regulated in laryngeal carcinoma tissues,which may be po-tential prognostic markers and therapeutic targets.