弥漫浸润型星形细胞瘤中PI3K、PTEN和GSK-3β的表达及临床意义

Expressions of PI3K,PTEN and GSK-3βin diffusely infiltrating astrocytomas and their clinical significance

目的:探讨磷酸肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)、糖原合成酶激酶3β(glycogen synthase kinase-3β,GSK-3β)和第10号染色体缺失的磷酸酶(homologous deletion phosphatasetensin on chromosome ten,PTEN)在弥漫浸润型星形细胞瘤中的表达及临床意义。方法:采用免疫组织化学法检测PI3K和GSK-3β在132例弥漫浸润型星形细胞瘤中的表达情况。应用荧光原位杂交技术标记PTEN在弥漫浸润型星形细胞瘤中的表达缺失情况。采用Kaplan-Meier生存曲线及COX比例风险回归模型对弥漫浸润型星形细胞瘤患者总生存期和预后因子进行单因素和多因素分析。结果:随着肿瘤WHO级别的升高,PI3K表达增加,而GSK-3β表达降低,差异均有统计学意义(P值均<0.05),且两者表达呈负相关(r=-0.424,P<0.05)。PTEN基因在弥漫型星形细胞瘤中未发生缺失,在间变型星形细胞瘤和胶质母细胞瘤中的缺失率分别为45%和30%。PI3K和GSK-3β的表达与肿瘤WHO分级和术后2年复发明显相关(P值均<0.05)。PI3K阳性患者的总生存率低于阴性患者,GSK-3β阳性患者的总生存率高于阴性患者(P值均<0.05)。WHO分级、PI3K阳性表达和GSK-3β阴性表达与弥漫浸润型星形细胞瘤患者的预后显著相关,其中WHO级别和PI3K阳性表达是影响弥漫浸润型星形细胞瘤患者预后的危险因素(P值均<0.05)。结论:弥漫浸润型星形细胞瘤中GSK-3β表达随着WHO级别的增高而降低,而PI3K表达随着WHO级别的增高而增高,PTEN在高级别的弥漫浸润型星形细胞瘤中发生缺失。

Objective:To investigate the expressions of phosphatidylinositol 3-kinase(PI3K),glycogen synthase kinase 3β(GSK-3β)and homologous deletion phosphatasetensin on chromosome ten(PTEN)in diffusely infiltrating astrocytomas,and to explore their clinical significance.Methods:Immunohistochemical method was used to detect the expressions of PI3K and GSK-3βin diffusely infiltrating astrocytomas.Fluorescence in situ hybridization was used to label the expression of PTEN in diffuse infiltrating astrocytomas.Kaplan-Meier survival curve and COX proportional hazard regression model were used to univariate and multivarite analysis of overall survival and prognosis.Results:The expression of PI3K in diffusely infiltrating astrocytomas increased with the increase of WHO grade,while the expression of GSK-3βdecreased with the increase of WHO grade,and the differences were statistically significant(both P<0.05).The expression of GSK-3βwas negatively correlated with the expression of PI3K in diffusely infiltrating astrocytomas.There was no deletion of PTEN gene in diffuse astrocytoma,but the deletion rates of anaplastic astrocytoma and glioblastoma were 45%and 30%,respectively.The expressions of PI3K and GSK-3βwere correlated with WHO grade and the recurrence two years after operation(all P<0.05).The results of Kaplan-Meier survival curve showed that the overall survival rate of PI3K positive patients was lower than that of the negative patients,and the overall survival rate of GSK-3βpositive patients was higher than that of the negative patients.Univariate analysis showed that WHO grade,the positive expression of PI3K and the negative expression of GSK-3βwere significantly correlated with the prognosis of patients with diffusely infiltrating astrocytomas.Multivariate analysis showed that WHO grade and the positive expression of PI3K were risk factors affecting the prognosis of patients with diffuse invasive astrocytoma(both P<0.05).Conclusion:The expression of GSK-3βin diffusely infiltrating astrocytomas decreased with the increase of WHO grade,the expression of PI3K increased with the increase of WHO grade,and the expression of PTEN was absent in high grade diffusely infiltrating astrocytomas.