PI3K/AKT/mTOR信号转导通路相关蛋白在脑胶质瘤中的表达及临床意义

目的研究PI3K/AKT/mTOR信号转导通路相关蛋白PI3K、mTOR、PTEN在脑胶质瘤中的表达及临床意义。方法采用免疫组化Envision二步法检测75例患者的脑胶质瘤标本(胶质瘤组,其中肿瘤分级Ⅱ级30例,Ⅳ级45例)及10名正常人(正常对照组)脑组织PI3K、mTOR、PTEN蛋白的表达,并对脑胶质瘤患者进行生存的相关分析。结果 PI3K、mTOR蛋白在胶质瘤组的阳性率显著高于正常对照组(均P<0.01),PTEN阳性率显著低于正常对照组(P<0.05)。Ⅱ级脑胶质瘤标本中PI3K、mTOR蛋白阳性率显著低于Ⅳ级(均P<0.01),PTEN阳性率显著高于Ⅳ级(P<0.05)。PTEN与PI3K、mTOR蛋白在胶质瘤中的表达分别呈负相关(r=-0.565,P=0.000;r=-0.322,P=0.005);PI3K与mTOR的表达呈正相关(r=0.456,P=0.000)。单因素分析显示,年龄、肿瘤级别、术后放化疗及PI3K蛋白表达影响患者术后的生存时间(r=-0.306,r=-0.422,r=0.392,r=-0.320;均P<0.05)。多因素回归分析显示,肿瘤级别、术后放化疗及PI3K蛋白表达为影响胶质瘤患者预后的独立因素(χ2=17.568,χ2=4.171,χ2=4.427;均P<0.05)。结论脑胶质瘤PI3K、mTOR的表达增高,PTEN的表达降低,并与肿瘤的恶性程度有关。肿瘤级别、术后放化疗及PI3K蛋白表达水平是影响胶质瘤患者预后的独立因素。

Expression and clinical significance of PI3K/AKT/mTOR signal transduction pathway related proteins in glioma

Objective To investigate the expression and clinical significance of PI3K/AKT/mTOR signal transduction pathway related proteins in glioma.Methods The expression of PI3K,mTOR and PTEN were detected by envision immunohistochemistry technique in glioma specimens from 75 patients(glioma group,including tumor grade Ⅱ in 30 cases and Ⅳ in 45 cases) and brian tissues from 10 normal controls(normal control group),and correlation analysis of survival was made.Result Compared with normal control group,the expression of PI3K,mTOR protein in glioma group were significantly higher(all P<0.01),and PTEN was significantly lower(P<0.05).The expression of PI3K,mTOR protein in glioma grade Ⅱ were significantly lower than grade Ⅳ(all P<0.01),and PTEN was significantly higher(P<0.05).The expression of PTEN was negatively correlated with PI3K and mTOR protein in glioma respectively(r=-0.565,P=0.000;r=-0.322,P=0.005);the expression of PI3K and mTOR protein were positively correlated(r=0.456,P=0.000).Univariate survival analysis showed that age,pathological grade,postoperative radiotherapy and chemotherapy,and the expression of PI3K protein were the influencing factors of survival time of patients(r=-0.306,r=-0.422,r=0.392,r=-0.320;all P<0.05).Multivariate regressiom analysis showed that pathological grade,postoperative radiotherapy and chemotherapy,PI3K protein expression were independent factors of prognosis of glioma patients(χ2=17.568,χ2=4.171,χ2=4.427;all P<0.05).Conclusions The expression of PI3K,mTOR protein are increased and PTEN expression was decreased in gliomas;which are closely correlated to the grade-malignancy.The pathological grade,postoperative radiotherapy and chemotherapy,expression of PI3K protein are the independent prognostic factors in patients with glioma.