pGSK-3α／β(Tyr279／216)和X连锁凋亡抑制蛋白在胆管癌中的表达及其临床意义  

Expression of pGSK-3oL/I5 （ Tyr279/216 ） and XIAP proteins in cholangiocarcinoma and theirclinical significance

作　　者：徐杰伟[1] 周凡[2] 蒋桂星[2] 陈城洋[2] 汪晶晶[2] 曹利平[1] 

机构地区：[1]湖州市中心医院普外科,313000 [2]浙江大学医学院附属第二医院外科

出　　处：《中华肿瘤杂志》2013年第5期366-371,共6页Chinese Journal of Oncology

基　　金：浙江省科技厅重大科技专项重点社会发展项目（2011C13034-2）

摘　　要：目的研究糖原合成激酶3（GSK-3）活性形式pGSK-3a／β（Tyr279／216）及其下游分子X连锁凋亡抑制蛋白（XIAP）在胆管癌组织中的表达情况，并探讨其表达与胆管癌临床病理特征及预后的关系。方法采用免疫组化法检测50例胆管癌组织和20例正常胆管组织中pGSK-3a／β（Tyr279／216）和XIAP蛋白的表达水平。结果pGSK-3a／β（Tyr279／216）和XIAP蛋白在胆管癌组织中阳性表达率分别为62．O％和68．0％，在正常胆管组织中的阳性表达率分别为10．0％和25．0％，pGSK-30a／β（Tyr279／216）和XIAP蛋白在胆管癌组织中的表达强度显著高于正常胆管组织（均P〈0．001）。Spearman相关分析显示，pGSK-3a／β（Tyr279／216）和XIAP蛋白在胆管癌组织中的表达具有显著相关性（r=0．544，P〈0．001）。pGSK-3a／β（Tyr279／216）蛋白表达与胆管癌的TNM分期（P=0．042）和组织分化程度（P=0．031）有关，XIAP蛋白表达与血清CEA水平有关（P=0．006）。pGSK-3a／β（Tyr279／216）阳性表达和阴性表达患者的5年生存率分别为3．2％和26．3％（P=0．002），XIAP阳性表达和阴性表达患者的5年生存率分别为5．9％和25．9％（P=0．018）。多因素分析结果显示，TNM分期（P=0．006）、术前总胆红素（P=0．001）、并发症（P=0．003）和pGSK-3a／β蛋白水平（P=0．002）是影响胆管癌患者预后的独立因素。结论pGSK-3a/β（Tyr279／216）和XIAP蛋白与胆管癌的发生、发展有密切关系，pGSK-30a／β（Tyr279／216）可作为预测胆管癌预后的重要因素。Objective To investigate the expressions of the active form of glycogen synthase kinase- 3 （ GSK-3 ） -pGSK-3a/β （Tyr279/216） and its downstream moleculor X-linked inhibitor of apoptosis protein （XIAP） in cholangiocarcinoma and to analyze their correlation with clinicopathological and survival significance. Methods Immunohistoehemistry was used to detect the expressions of the active form of GSK- 3- pGSK-3a/β （Tyr279/216） and its downstream moleculor XIAP proteins in 50 cholangiocarcinoma tissues and 20 normal bile duct tissues. Results The positive rates of pGSK-3a/β （Tyr279/216） and XIAP were 62.0% and 68.0% in cholangiocarcinoma, and 10.0% and 25.0% in normal bile duct tissues, respectively. The intensity of pGSK-3a/β （Tyr279/216） and XIAP expressions in cholangiocarcinoma were significantly higher than that in the normal bile duct tissues （ P 〈 0. 001 ）, and there was a significant correlation between pGSK-3a/β （ Tyr279/216 ） and XIAP expressions （ r = 0. 544, P 〈 0. 001 ）. The expression of pGSK-3a/β（Tyr279/216） protein in cholangiocarcinoma was associated with TNM stage （P = 0.042）, histological grade （ P = 0.031 ）, whereas the expression of XIAP protein in cholangiocarcinoma was correlated with CEA level （P =0. 006）. Patients with positive expression of pGSK-3a/[3 （Tyr279/216） and XIAP demonstrate a significantly worse prognosis than that of patients with negative expression of pGSK-3a/β （Tyr279/216） and XIAP for overall survival （P = 0. 002, P = 0. 018）. Multivariate survival analysis revealed that positive pGSK-3a/β （Tyr279/216） expression provided significant independent prognostic value for overall survival （P =0. 002）. Conclusions The expressions of pGSK-3a/β（Tyr279/216） and XIAP proteins were significantly associated with the development and progression of cholangiocarcinoma.pGSK-3a/β（Tyr279/216） may be an important prognostic factor for survival of patients with eholangioearcinoma.

关 键 词：胆管肿瘤 糖原合成激酶3 X连锁细胞凋亡抑制蛋白 免疫组织化学 预后 

分 类 号：R735.8[医药卫生—肿瘤]