星形胶质细胞瘤组织中PI3K、PTEN和GSK-3β的表达及临床意义

摘要/Abstract

摘要： 目的探讨磷脂酰肌醇3激酶（PI3K）、第10号染色体缺失的磷酸酶（PTEN）和糖原合成酶激酶（GSK）-3β在星形胶质细胞瘤组织中的表达及与临床病理特征和预后的关系。方法收集2014年1月至2018年12月星形胶质细胞瘤组织标本80例和正常脑组织标本20例，采用免疫组化法和实时荧光定量PCR（qPCR）法检测PI3K、PTEN和GSK-3β在上述组织中的表达。分析三者表达与临床病理特征和总生存时间（OS）的关系。三者间相关性分析采用Spearman法，多因素分析采用Cox比例风险回归模型。结果免疫组化染色显示，PI3K的表达随着星形胶质细胞瘤WHO分级的升高而增加（P=0.109），GSK-3β和PTEN的表达随着WHO分级的升高而降低（P=0.029，P=0.033）。qPCR检测显示，PI3K mRNA的相对表达量随着星形胶质细胞瘤WHO分级的升高而增加（P=0.158），PTEN mRNA和GSK-3β mRNA的相对表达量随着WHO分级的升高而降低（P=0.038,P=0.029）。PI3K与PTEN和GSK-3β的表达呈负相关（r=-0.263，P=0.018；r=-0.285，P=0.010）；PTEN与GSK-3β的表达无关（r=0.056，P=0.620）。PI3K表达与临床病理参数均无关（P>0.05）；PTEN和GSK-3β的表达与WHO分级和IDH-1表达有关（P＜0.05），与年龄、性别和GFAP、Vimentin的表达无关（P>0.05）。PI3K阳性表达组1、2年生存率分别为57.1%和31.0%，低于阴性表达组的79.0%和71.1%（P=0.001）；GSK-3β阳性表达组1、2年生存率分别为74.4%和61.5%，高于阴性表达组的61.0%和39.0%（P=0.049）；PTEN阳性表达组1、2年生存率分别为74.9%和62.9%，高于阴性表达组的53.3%和23.3%（P=0.270）。单因素分析显示，WHO分级、PI3K表达和GSK-3β表达与星形胶质细胞瘤患者的OS有关（P＜0.05）。Cox多因素分析显示，PI3K表达是影响星形胶质细胞瘤患者OS的独立因素（P=0.001）。结论 PI3K水平随着星形胶质细胞瘤WHO分级的升高而增加，PTEN和GSK-3β水平随着星形胶质细胞瘤WHO分级的升高而降低。PI3K阳性表达者以及PTEN和GSK-3β阴性表达者的预后较差。三者可能参与了星形胶质细胞瘤的发生发展，对预测预后有一定价值。

关键词: 星形胶质细胞瘤, 磷脂酰肌醇3激酶, 第10号染色体缺失的磷酸酶, 糖原合成酶激酶-3β

Abstract: Objective To investigate the expression of phosphatidylinositol 3 kinase (PI3K), phosphatase deleted on chromosome 10 (PTEN) and glycogen synthase kinase (GSK)-3β in astrocytoma and its relationship with clinicopathological features and prognosis. Methods Eighty astrocytoma tissue samples and 20 normal brain tissue samples were collected from January 2014 to December 2018,PI3K, PTEN and GSK-3βexpression in the above tissues were detected by immunohistochemistry and real-time fluorescence quantitative PCR (qPCR). The relationship between their expression and clinicopathological features and overall survival(OS) was analyzed. Spearman method was used for correlation analysis, and Cox proportional hazards regression model was used for multivariate analysis. Results Immunohistochemical staining showed that the expression of PI3K increased with the increase of astrocytoma WHO grade (P=0.109), the expression of GSK-3βand PTEN decreased with the increase of WHO grade (P=0.029, P=0.033). qPCR showed that the relative expression of PI3K mRNA increased with the increase of astrocytoma WHO grade (P=0.158), and the relative expression of PTEN mRNA and GSK-3β mRNA decreased with the increase of astrocytoma WHO grade（P=0.038,P=0.029）. PI3K was negatively correlated with PTEN and GSK-3β(r=-0.263, P=0.018; r=-0.285, P=0.010); GSK-3β was not related to the expression of PTEN (r=0.056, P=0.620). The expression of PI3K was not related to clinicopathological parameters (P>0.05); The expression of PTEN and GSK-3β was related to WHO grade and IDH-1 expression (P<0.05), but not to age, sex and the expression of GFAP and Vimentin (P>0.05). The 1-year and 2-year survival rates of PI3K positive expression group were 57.1% and 31.0%, respectively, lower than 79.0% and 71.1% of negative expression group (P=0.001); The 1-year and 2-year survival rates in GSK-3β positive expression group were 74.4% and 61.5% respectively, which were higher than 61.0% and 39.0% in negative expression group (P=0.049); The 1-year and 2-year survival rates of PTEN positive expression group were 74.9% and 62.9% respectively, which were higher than 53.3% and 23.3% of negative expression group (P=0.270). Univariate analysis showed that WHO grade, and the expression of PI3K and GSK-3β were related to OS in patients with astrocytoma (P<0.05). Cox multivariate analysis showed that PI3K expression was the independent factor affecting OS in patients with astrocytoma (P=0.001). Conclusion The level of PI3K increases with the increase of astrocytoma WHO grade, and the level of PTEN and GSK-3β decreases with the increase of WHO grade. The prognosis of patients with PI3K positive expression, and negative expression of PTEN and GSK-3β is poor. They may be involved in the occurrence and development of astrocytoma and have a certain value in predicting the prognosis.

Key words: Astrocytoma, Phosphatidylinositol 3 kinase, Phosphatase deleted on chromosome 10, Glycogen synthase kinase-3β

李木子, 高勤, 石柳, 罗克莲. 星形胶质细胞瘤组织中PI3K、PTEN和GSK-3β的表达及临床意义 [J]. 临床肿瘤学杂志, 2022, 27(03): 193-200.

LI Muzi, GAO Qin, SHI Liu, LUO Kelian. Expression and clinical significance of PI3K, PTEN and GSK-3β in astrocytoma[J]. Chinese Clinical Oncology, 2022, 27(03): 193-200.

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