PTEN/PI3K/AKT在溃疡性结肠炎炎症-肿瘤序列演进中的作用

目的 观察抑癌基因第10号染色体缺失的磷酸酶和张力蛋白同源物基因(PTEN)与磷脂酰肌醇3激酶(PI3K)/丝氨酸苏氨酸蛋白激酶(AKT)信号通路在溃疡性结肠炎(UC)炎症-肿瘤序列演进过程中的表达变化,为阐明UC的发生及其癌变机制提供依据,并探讨其可能的临床意义.方法 收集65例UC的石蜡包埋标本、25例结直肠癌石蜡包埋标本、25例正常组织石蜡包埋标本,采用免疫组织化学染色法检测UC、结直肠癌及正常组织中PTEN及AKT的蛋白表达,并分析它们之间的相关关系.结果 ①UC组织中PTEN蛋白的表达明显低于正常组织,高于结直肠癌组织(P<0.01).②UC组织中AKT蛋白的表达明显高于正常组织,低于结直肠癌组织(P<0.01).③随着UC病程的增加,PTEN蛋白的表达逐渐降低,AKT蛋白的表达逐渐增强(P<0.01).④PTEN蛋白和AKT蛋白在UC、结直肠癌组织中的表达呈显著负相关(相关系数分别为r=-0.542、-0.674,P<0.01).结论 在UC炎症-肿瘤序列演进过程中,抑癌基因PTEN蛋白表达的降低及原癌基因AKT蛋白表达的增强,可能是UC发生及癌变的重要原因之一.PTEN蛋白表达的明显降低和AKT蛋白表达的明显增强有可能成为早期监测UC癌变的一个辅助指标.

Change from Inflammation to Carcinoma in Ulcerative Colitis: the Role of PTEN/PI3K/AKT

Objective To detect the changes of expression of PTEN protein and AKT protein in patients with Ulcerative Colitis (UC) in the pathway from inflammation to carcinoma. Methods A total of 110 paraffin colorectal sections were examined, which included 65 cases with UC. 25 cases with colorectal cancer and 25 cases with normal tissues. The expression of PTEN protein and AKT protein was detected with immunohistochemistry. Results ① The patients with UC had lower expression of PTEN protein and higher expression of AKT than those with normal tissues (P<0. 01). ② The patients with UC had higher expression of PTEN protein and lower expression of AKT protein than those with colorectal cancer (P<0.01). ③ With the progress of UCthe expression of PTEN protein decreased while the expression of AKT protein increased (P<0. 01). ④ The expression of PTEN protein was negatively correlated with the expression with AKT protein in patients with UC and colorectal cancer (r=-0. 542 and-0. 674,respectively P<0. 01). Conclusion The change of expressions of PTEN protein and AKT protein might play an important role in the development of UC and colorectal cancer. Decreased PTEN protein and increased AKT protein might be a marker for the early detection of the occurrence of colorectal cancer in patients with UC.