PI3K/Akt/mTOR信号传导通路与人脑胶质瘤恶性进展及预后的相关研究

摘要

目的 探讨磷脂酰肌醇3-激酶(PI3K),磷酸化蛋白激酶B(p-AKT)和磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)在人脑胶质瘤组织中的表达及其与人脑胶质瘤恶性进展和预后的相关性.方法 选取南京医科大学附属淮安第一医院神经外科自2004年9月至2008年9月间手术切除并经病理证实的人脑胶质瘤标本88例,另取非肿瘤组织中的正常脑组织标本20例作为对照.采用免疫组织化学染色检测脑胶质瘤组织和正常脑组织中PI3K、p-AKT及p-mTOR的表达,并统计分析其与患者的临床病理学特征及预后的关系.结果 PI3K、p-AKT、p-mTOR在脑胶质瘤组织中的阳性表达率均显著高于正常脑组织,差异有统计学意义(PI3K:x2=14.028,P=0.009;p-AKT:x2=15.132,P=0.008和mTOR:x2=15.293,P=0.008);不同病理分级、治疗前KPS评分以及临床分期脑胶质瘤组织中PI3K、p-AKT和p-mTOR阳性表达率的差异均有统计学意义(P＜0.05);PI3K、p-AKT、p-mTOR阳性表达组患者的5年总体生存率均显著低于其阴性表达组(PI3K:x2=8.381,P=0.026;p-AKT:x2=12.923,P=0.011;mTOR:x2=13.252,P=0.013).结论 PI3K/Akt/mTOR信号传导通路在脑胶质瘤组织中被过度激活,与肿瘤的恶性程度密切相关,可以作为判断脑胶质瘤患者预后的生物学指标.%Objective To investigate the protein expression of phosphatidylinositol 3-kinase (PI3K), phosphorylated Akt B (p-Akt) and p-mTOR in human gliomas, and evaluate their clinical significance in clinicopathological status and prognosis of these patients with gliomas. Methods Eighty-eight patients, admitted to our hospital from September 2004 to September 2008, were chosen in our study; these patients were performed surgical resection and the samples were pathologically confirmed as gliomas. Another 20 samples, cut from the normal brain tissue were adopted as controls.Immunohistochemistry was employed to examine the protein expression of PI3K, p-AKT and p-mTOR.Then, the correlation of their expression with the clinicopathological features of the gliomas and prognosis of the patients was further analyzed. Results The positive expression rates of PI3K in gliomas and normal brain tissues were 68.18% (60/88) and 18.18% (16/88), respectively; those of p-AKT were 73.86% (65/88) and 17.05% (15/88), respectively;, those of p-mTOR were 75.00% (66/88) and 18.18% (16/88), respectively; the expression levels of these 3 proteins were all significantly higher than those in normal brain tissues (PI3K: x2=14.028, P=0.009; p-AKT: x2=15.132, P=0.008 and mTOR:x2=15.293, P=0.008). The positive expression rates of PI3K, p-AKT and p-mTOR were significantly different in the gliomas with pathological grades, different scores of Karnofsky performance status and different clinical stages (P＜0.05). In addition, the 5-year overall survival rate in PI3K-positive group,p-AKT-positive group and p-mTOR-positive group was significantly lower than in those negative groups (PI3K: x2=8.381, P=0.026; p-AKT: x2=12.923, P=0.011; mTOR: x2=13.252, P=0.013). Conclusion PI3K/Akt/mTOR signal transduction pathway is over-activated in gliornas, which is closely correlated to the grade-malignancy; and the positive expression of PI3K, p-AKT and p-mTOR may predict the poor prognosis of the patients with gliomas.