PI3K、Akt以及PTEN在胃肠道间质瘤中的表达及意义

目的:探讨PI3K、Akt以及PrEN的表达与GIST临床病理特征及预后的相关性,并探讨它们间的相互关系,以揭示其在GIST发生发展过程中的作用,为进一步的肿瘤靶点治疗提供理论依据.方法:选择临床病理资料完整、随访结果确切的中国医科大学附属盛京医院1990年-2007年2月手术切除、病理证实的GIST新鲜组织标本124例.男性64例、女性60例,平均年龄54.6岁.RT-PCR检测PI3K、Akt以及PTEN在GIST及对照组的mRNA水平.结果:PI3K mRNA水平随NIH分级表达上调(P＜0.05),PI3K的阳性表达率与黏膜受侵和肿瘤侵袭转移均显著相关(P＜0.05).Akt mRNA水平随NIH分级表达上调,其中在高、中危肿瘤组之间不明显,无统计学意义,其余各组有意义；Akt的阳性表达率与肿瘤侵袭转移和黏膜受侵显著相关,提示Akt的过表达促进了GIST的肿瘤侵袭转移.同时PTENmRNA随NIH分级表达下调(P＜0.05),随着肿瘤恶性程度的增加,PTEN的缺失率增高；PTEN的阳性表达率与肿瘤侵袭转移和黏膜受侵关系密切.结论:PI3 K/Akt与PTEN在GIST的发生发展中可能互相拮抗共同作用,PI3K、Akt蛋白阳性表达之间呈显著正相关(r =0.292.P=0.031)；PI3K与PTEN蛋白阳性表达之间呈显著负相关(r=-0.412,P =0.036)；PTEN与Akt蛋白阳性表达之间呈显著负相关(r=-0.386,P=0.024).

Expression and significance of PI3K, Akt and PTEN in gastrointestinal stromal tumors

Objectives:To study the mRNA changes of PI3K,Akt and PTEN,further discussing the changes of factors at expression level and their relationship with clinical pathologic characteristics and prognosis of GIST.Methods: The 124 fresh samples of GIST patients(64 males and 60 females) were acquired from the Shengjing Hospital of China Medical University from 1990 to 2007.mRNA levels in GIST and control were detected by RT-PCR.Results:The up-regulated expression of PI3K mRNA presented with the increasing of NIH grades(P<0.05).The expression rate of PI3K was significantly associated with the invasion of mucosa and lymph node metastasis(P<0.05).We also found that the up-regulated expression of Akt mRNA presented with the increasing of NIH grades except that between high risk group and moderate risk group.The expression rate of Akt was significantly associated with mucosa invasion and lymph metastasis.The down-regulated expression of PTEN mRNA presented with the increasing of NIH grades(P<0.05),and the deficient rate of PTEN was higher with the severer malignancy of the tumor.The expression rate of PTEN was closely associated with mucosa invasion and lymph metastasis.Conclusion:In gastrointestinal stromal tumors,the tumor suppressor gene-PTEN is reduced with PI3K and Akt increasing.The positive expression rate of PTEN,PI3K and Akt have relationship with lymphatic metastasis and mucosal invasion.PI3K/Akt and PTEN maybe have the role of mutual antagonism in GIST occurrence and development.