【摘要】：目的SUMO是一類在結(jié)構(gòu)上與泛素相似的蛋白,它不僅參與蛋白的翻譯后修飾、調(diào)節(jié)細(xì)胞代謝過程,同時(shí)在DNA損傷修復(fù)和維持基因組完整性中也發(fā)揮著重要作用。研究表明SUMO化途徑的失調(diào)與多種腫瘤的發(fā)生、發(fā)展過程密不可分。SUMO激活酶E1是SUMO化過程中唯一的激活酶,而SAE2為SUMO激活酶E1必不可少的重要組成亞基,其表達(dá)異�？梢餝UMO化途徑的紊亂,為腫瘤的發(fā)生、發(fā)展提供有利條件。本實(shí)驗(yàn)通過檢測膽管癌與正常膽管組織中SAE2的表達(dá)差異,探討SAE2的表達(dá)與膽管癌患者臨床病理因素及其預(yù)后的關(guān)系,為評(píng)估膽管癌患者的預(yù)后及開創(chuàng)新的治療方向提供理論依據(jù)。方法收集青島大學(xué)附屬醫(yī)院2009年1月—2011年12月期間經(jīng)手術(shù)切除后石蠟包埋的膽管病理組織標(biāo)本80例,其中膽管癌組織標(biāo)本60例,正常膽管組織標(biāo)本20例。用PV-6000免疫組織化學(xué)法檢測SAE2在膽管癌及正常膽管組織中的表達(dá)情況,隨訪60例膽管癌患者的生存情況,并應(yīng)用Kaplan-meier單因素生存分析及Cox多因素回歸分析探討SAE2的表達(dá)與膽管癌患者臨床病理因素及預(yù)后的關(guān)系。結(jié)果1.SAE2在膽管癌和正常膽管組織中的陽性表達(dá)率分別為71.67%(43/60)和30.00%(6/20),差異有統(tǒng)計(jì)學(xué)意義(χ2=10.972,P0.001);2.SAE2的表達(dá)與膽管癌患者腫瘤的分化程度、TNM分期密切相關(guān)(P0.05),與患者年齡、性別、腫瘤大小及腫瘤所在部位無相關(guān)性(P0.05);3.Kaplan-meier生存分析顯示:膽管癌患者的的生存率與SAE2的表達(dá)水平及TNM分期有關(guān)(P0.05),與腫瘤的病理分化程度無關(guān)(P0.05)。Cox多因素回歸分析顯示:SAE2的表達(dá)水平以及腫瘤的TNM分期為膽管癌患者預(yù)后的獨(dú)立影響因素。SAE2低表達(dá)的患者生存率高于SAE2高表達(dá)的患者;TNM分期較早的患者生存率高于分期晚的患者,且生存時(shí)間隨TNM分期的遞增而明顯下降。結(jié)論SAE2在膽管癌組織中的表達(dá)水平明顯高于正常膽管組織,且與膽管癌患者的TNM分期、腫瘤的分化程度有關(guān);SAE2的表達(dá)水平和TNM分期是膽管癌患者預(yù)后的獨(dú)立影響因素。SAE2低表達(dá)的患者生存率高于SAE2高表達(dá)的患者;TNM分期較早的患者生存率高于分期較晚的患者,提示SAE2的異常表達(dá)可能參與了膽管癌的發(fā)生、發(fā)展及浸潤過程,并且與患者的預(yù)后密切相關(guān)。
[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.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.8

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本文編號(hào)：2160916