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SAE2在胆管癌中的表达及其临床意义

发布时间:2018-08-03 06:55
【摘要】:目的SUMO是一类在结构上与泛素相似的蛋白,它不仅参与蛋白的翻译后修饰、调节细胞代谢过程,同时在DNA损伤修复和维持基因组完整性中也发挥着重要作用。研究表明SUMO化途径的失调与多种肿瘤的发生、发展过程密不可分。SUMO激活酶E1是SUMO化过程中唯一的激活酶,而SAE2为SUMO激活酶E1必不可少的重要组成亚基,其表达异常可引起SUMO化途径的紊乱,为肿瘤的发生、发展提供有利条件。本实验通过检测胆管癌与正常胆管组织中SAE2的表达差异,探讨SAE2的表达与胆管癌患者临床病理因素及其预后的关系,为评估胆管癌患者的预后及开创新的治疗方向提供理论依据。方法收集青岛大学附属医院2009年1月—2011年12月期间经手术切除后石蜡包埋的胆管病理组织标本80例,其中胆管癌组织标本60例,正常胆管组织标本20例。用PV-6000免疫组织化学法检测SAE2在胆管癌及正常胆管组织中的表达情况,随访60例胆管癌患者的生存情况,并应用Kaplan-meier单因素生存分析及Cox多因素回归分析探讨SAE2的表达与胆管癌患者临床病理因素及预后的关系。结果1.SAE2在胆管癌和正常胆管组织中的阳性表达率分别为71.67%(43/60)和30.00%(6/20),差异有统计学意义(χ2=10.972,P0.001);2.SAE2的表达与胆管癌患者肿瘤的分化程度、TNM分期密切相关(P0.05),与患者年龄、性别、肿瘤大小及肿瘤所在部位无相关性(P0.05);3.Kaplan-meier生存分析显示:胆管癌患者的的生存率与SAE2的表达水平及TNM分期有关(P0.05),与肿瘤的病理分化程度无关(P0.05)。Cox多因素回归分析显示:SAE2的表达水平以及肿瘤的TNM分期为胆管癌患者预后的独立影响因素。SAE2低表达的患者生存率高于SAE2高表达的患者;TNM分期较早的患者生存率高于分期晚的患者,且生存时间随TNM分期的递增而明显下降。结论SAE2在胆管癌组织中的表达水平明显高于正常胆管组织,且与胆管癌患者的TNM分期、肿瘤的分化程度有关;SAE2的表达水平和TNM分期是胆管癌患者预后的独立影响因素。SAE2低表达的患者生存率高于SAE2高表达的患者;TNM分期较早的患者生存率高于分期较晚的患者,提示SAE2的异常表达可能参与了胆管癌的发生、发展及浸润过程,并且与患者的预后密切相关。
[Abstract]:Objective SUMO is a class of proteins that are structurally similar to ubiquitin. It not only participates in the post-translational modification of proteins and regulates the metabolic process of cells, but also plays an important role in the repair of DNA damage and maintenance of genomic integrity. The study shows that the imbalance of SUMO pathway is closely related to the occurrence of many kinds of tumors. Sumo activator E1 is the only activating enzyme in the process of SUMO, and SAE2 is an essential component subunit of SUMO activase E1. Abnormal expression of SUMO may lead to disorder of SUMO pathway and provide favorable conditions for tumor occurrence and development. The purpose of this study was to investigate the relationship between the expression of SAE2 and clinicopathological factors and prognosis of patients with cholangiocarcinoma by detecting the difference of SAE2 expression between cholangiocarcinoma and normal bile duct tissues. To evaluate the prognosis of patients with cholangiocarcinoma and to create a new treatment direction. Methods from January 2009 to December 2011, 80 specimens of paraffin embedded bile duct were collected from affiliated Hospital of Qingdao University, including 60 cases of cholangiocarcinoma and 20 cases of normal bile duct. The expression of SAE2 in cholangiocarcinoma and normal bile duct tissues was detected by PV-6000 immunohistochemical method. The survival status of 60 patients with cholangiocarcinoma was followed up. The relationship between the expression of SAE2 and clinicopathological factors and prognosis in patients with cholangiocarcinoma was investigated by Kaplan-meier single factor survival analysis and Cox multivariate regression analysis. Results the positive expression rates of 1.SAE2 in cholangiocarcinoma and normal bile duct tissues were 71.67% (43 / 60) and 30.00% (6 / 20) respectively. There was no correlation between tumor size and tumor location (P0.05). Kaplan-meier survival analysis showed that the survival rate of cholangiocarcinoma patients was related to SAE2 expression and TNM stage (P0.05), but not to the degree of pathological differentiation of the tumor (P0.05) .Cox multivariate regression analysis showed that the survival rate of cholangiocarcinoma patients was related to the expression level of SAE2 and TNM stage (P0.05). The survival rate of patients with low expression of SAE2 was higher than that of patients with high expression of SAE2, and the survival rate of patients with earlier stage of SAE2 was higher than that of patients with late stage. The survival time decreased with the increase of TNM stage. Conclusion the expression of SAE2 in cholangiocarcinoma tissues is significantly higher than that in normal bile duct tissues, and it is associated with the TNM staging in patients with cholangiocarcinoma. The survival rate of patients with low expression of SAE2 was higher than that of patients with high expression of SAE2, and the survival rate of patients with earlier stage of SAE2 was higher than that of patients with late stage. These results suggest that the abnormal expression of SAE2 may be involved in the occurrence, development and invasion of cholangiocarcinoma, and may be closely related to the prognosis of the patients.
【学位授予单位】:青岛大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R735.8

【参考文献】

相关期刊论文 前2条

1 Yasuni Nakanuma;Yasunori Sato;Kenichi Harada;Mokoto Sasaski;Hiroko Ikeda;;Pathological classification of intrahepatic cholangiocarcinoma based on a new concept[J];World Journal of Hepatology;2010年12期

2 李灼日;吴金术;毛先海;田秉璋;;C-myc、P16和Bc1-2蛋白在胆管癌中表达及意义[J];中国现代医学杂志;2006年22期



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