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目的探讨人滋养层细胞表面抗原-2(human trophoblast cell-surface antigen 2,TROP2)、磷酸酶与张力蛋白同源物(phosphatase and tensin homolog,PTEN)、磷酸化蛋白激酶B(phosphorylated protein kinase B,p-AKT)在胆囊癌组织中的表达情况、相互关系及临床意义。方法收集我院2003年1月至2009年12月期间确诊并手术的胆囊癌患者71例,获得胆囊癌组织标本71例及癌旁组织15例。采用免疫组织化学法检测TROP2、PTEN和p-AKT的表达,χ~2检验分析TROP2、PTEN和p-AKT蛋白表达水平与临床病理参数之间的关系,Spearman检验法分析TROP2、PTEN和p-AKT间两两相关性。结果 (1)与癌旁组织比,TROP2和p-AKT蛋白在胆囊癌组织中的阳性表达率明显升高(P<0.05),而PTEN蛋白在胆囊癌组织中的阳性表达率明显降低(P<0.05);(2)TROP2、PTEN和p-AKT三种蛋白的表达与胆囊癌患者的性别、年龄均无关(P>0.05),但与胆囊结石、分化程度、其他脏器侵犯、浸润深度及TNM分期相关(P<0.05);(3)TROP2与p-AKT呈正相关(P<0.05),但两者与PTEN呈负相关(P<0.05)。结论 TROP2/PTEN/p-AKT信号通路异常激活可能是胆囊癌恶性进展的重要原因,其机制可能涉及TROP2对PTEN及p-AKT的调控作用,这为临床上靶向干预胆囊癌研究提供理论基础。
Objective To investigate the expression of human trophoblast cell-surface antigen 2 (TROP2), phosphatase and tensin homolog (PTEN), phosphorylated protein kinase B p-AKT) in gallbladder cancer tissues, their relationship and clinical significance. Methods Totally 71 patients with gallbladder carcinoma diagnosed and operated from January 2003 to December 2009 in our hospital were collected, and 71 cases of gallbladder carcinoma tissues and 15 cases of adjacent tissues were obtained. The expressions of TROP2, PTEN and p-AKT were detected by immunohistochemistry. The relationship between TROP2, PTEN and p-AKT protein expression and clinical pathological parameters was analyzed byχ ~ 2 test. Spearman test was used to analyze the expression of TROP2, PTEN and p- AKT between any two correlations. Results (1) The positive expression rate of TROP2 and p-AKT protein in gallbladder carcinoma tissues was significantly higher than that in adjacent tissues (P <0.05), while the positive expression rate of PTEN protein in gallbladder carcinoma tissues was significantly lower (P <0.05). (2) The expressions of TROP2, PTEN and p-AKT were not related to the gender and age of patients with gallbladder cancer (P> 0.05), but correlated with gallstone, differentiation, invasion of other organs, depth of invasion (P <0.05); (3) There was a positive correlation between TROP2 and p-AKT (P <0.05), but negatively correlated with PTEN (P <0.05). Conclusion The abnormal activation of TROP2 / PTEN / p-AKT signaling pathway may play an important role in the malignant progression of gallbladder carcinomas. The mechanism may be related to the regulatory effect of TROP2 on PTEN and p-AKT, which may provide the theoretical basis for the targeted clinical intervention in gallbladder cancer .