PI3K、AKT、PTEN在脑胶质瘤中的表达及其临床意义

Expression of PI3K,AKT and PTEN Protein in Human Glioma and their Clinical Significance

背景与目的:PI3K/AKT信号通路可能在人脑恶性胶质瘤的发生发展过程中起重要作用。本研究探讨人脑胶质瘤中PI3K/AKT通路相关蛋白PI3K、AKT、PTEN在脑胶质瘤中的表达及其与胶质瘤病理分级之间的关系。方法:采用免疫组化Envision二步法检测PI3K、AKT、PTEN蛋白在42例不同级别脑胶质瘤、10例正常脑组织中的表达,计算阳性细胞百分率,用统计学方法分析人脑胶质瘤中PI3K、AKT、PTEN蛋白表达之间的相关性及其三者与胶质瘤不同分级之间的关系。结果:PI3K在人脑胶质瘤组织的阳性表达率是80.95%,而正常脑组织中表达率为20.00%,两者间差异有统计学意义(P<0.05);PI3K蛋白在低级别胶质瘤和高级别胶质瘤中的阳性率分别是66.67%、95.24%,两者之间差异有统计学意义(P<0.05)。胶质瘤组织与正常脑组织中AKT蛋白阳性率分别是85.71%与30.00%,两者差异有统计学意义(P<0.05);AKT蛋白在低级别胶质瘤和高级别胶质瘤中的阳性率分别是76.19%与95.24%,两者之间差异有统计学意义(P<0.05);胶质瘤组织与正常脑组织中PTEN蛋白阳性率分别是45.24%、100%,两者差异有统计学意义(P<0.01);PTEN蛋白在低级别胶质瘤中的阳性率52.38%,而高级别胶质瘤表达率为38.10%,两者之间差异有显著性(P<0.05);PTEN与PI3K、AKT蛋白在脑胶质瘤中的表达分别呈负相关(P<0.01);PI3K与AKT蛋白的阳性表达呈正相关(P<0.01)。结论:(1)在人脑胶质瘤组织中PI3K、AKT蛋白表达明显增高,且PI3K、AKT蛋白阳性表达与胶质瘤恶性程度正相关,说明了PI3K/AKT信号通路在胶质瘤的恶性转化中发挥着重要作用。(2)胶质瘤组织中PTEN蛋白的阳性表达率明显低于其在正常脑组织中的表达,与胶质瘤的恶性程度负相关,提示了PTEN蛋白的表达下降或缺失导致其抑癌功能减弱甚至丧失,其与胶质瘤的发生发展密切相关。(3)在人脑胶质瘤组织中,PTEN与PI3K、AKT蛋白表达呈负相关,揭示了在胶质瘤的发生发展中PTEN与PI3K、AKT的作用可能互相拮抗,PTEN蛋白的表达下降或缺失与PI3K、AKT的过度表达可能共同促进了胶质瘤的恶性进展。

BACKGROUND OBJECTIVE：The activation of PI3K/AKT passway plays an important role in the initiation and progression of human gliomas.In this study,we investigated the expression of the expression of PI3K/AKT signaling pathway correlated protein-PI3K,AKT and PTEN in human gliomas and its relationship to pathology grading.We also studied the relationship among PI3K,AKT,PTEN and the role they play in humam glioma tumorigenesis.METHODS：Envision Immunohistochemistry technique was applied to detect the expression of PI3K,AKT and PTEN in 42 formalin-fixed paraffin embedded samples of gliomas and 10 cases of normal brain tissue.Percentage of positive expressed cells were calculated.The relationship among PI3K,AKT and PTEN in human gliomas and its relationship to pathology grading were analyzed.RESULTS：The expression of PI3K protein in glioma tissue was 80.95% and 20.00% in nomal brain tissue（P 0.05）,respectively.The expression of PI3K protein in low-grade gliomas and high-grade gliomas was 66.67% and 95.24% respectively（P 0.05）.Akt protein expression in glioma tissue and normal brain tissue were 85.71% and 30.00%,respectively.The Akt protein expression in low-grade gliomas and high-grade were 76.19% and 95.24%（P 0.05）,respectively.The positive expression of PTEN was found in 45.24% of glioma tissue and 100% of normal brain tissue（P 0.01）.PTEN protein in low-grade gliomas the expression rate is 52.38%,while the expression rate is 38.10% in the high-grade glioma（P 0.05）.Significant difference between low-grade and high-grade group was observed（P 0.05）.In 42 cases of brain glioma,a negative correlation was found between the expression of PTEN and PI3K or AKT protein expression respectively（both P 0.01）,and there was a positive correlation between PI3K and AKT protein expression（P 0.01）.CONCLUSIONS：PI3K and AKT expression were greatly increased with the asceding of tumor grade and correlated with the proliferation of gliomas The expression level of PTEN was significantly lower than in normal brain tissue,and it is negative correlated with the tumor grade In human glioma tissues,PTEN and PI3K,AKT protein expression was negatively correlated.The PI3K/AKT pathway is closely related to the occurrence and development of glioma,so it will be possible tu improve the effect of cancer therapy.