差异蛋白在脑胶质瘤中的表达及其相关性研究

Expression and correlation of differential proteins in glioma

摘要:

目的探讨脑胶质瘤中的差异蛋白的表达并筛选有临床价值的生物标志物。方法应用蛋白组学检测10对脑胶质瘤及配对瘤旁组织差异表达的蛋白，并采用免疫组织化学法验证差异蛋白在66例脑胶质瘤组织及正常脑组织中的表达情况。χ2检验差异蛋白的表达水平与脑胶质瘤患者临床、病理特征之间的关系；KaplanMeier回归模型分析差异蛋白与患者预后的关系，并绘制生存曲线。结果蛋白组学分析发现与瘤旁组织相比，有22个蛋白质在脑胶质瘤组织明显表达异常（上调13个，下调9个）。筛选差异表达最明显的4个蛋白GLUD1、VIM、PRDX1及MAT1A，采用免疫组织化学验证4种蛋白在脑胶质瘤组织及正常脑组织中的表达情况。结果显示与正常脑组织相比，胶质瘤组织中GLUD1（P=0.006）与PRDX1（P<0.001）表达明显上调，而MAT1A表达明显下调（P=0.001），VIM的表达无统计学差异（P=0.118）。与临床病理特征相关性分析显示，PRDX1表达水平与胶质瘤病理分级(P=0.008)及患者生存情况(P=0.004)明显相关，而与年龄、性别及胶质瘤直径无明显相关性(P>0.05)。GLUD1及MAT1A的表达与年龄、性别、病理分级、胶质瘤直径及生存率无明显相关性(P>0.05)。PRDX1高表达组和低表达组3年生存率分别为27.4%及57.1%，两组比较差异具有统计学意义(P=0.011)。结论差异蛋白中PRDX1在人脑胶质瘤组织中表达上调，并与病理分级、不良预后显著相关，可能是胶质瘤潜在的标志物。

关键词:脑胶质瘤|生物标志物|蛋白质组学|差异蛋白

Abstract:

ObjectiveTo investigate differentially expressed proteins in glioma and screen valuable clinical biomarkers.MethodsProteomics were used to detect 10 differentially expressed proteins in specimens of gliomas and paired paraneoplastic tissues. Immunohistochemistry was used to verify the expression of differential proteins in 66 glioma tissues and 30 normal brain tissues. Chisquare test was adopted to study the relationships between the expression level of differential proteins and the clinicopathological features of glioma. KaplanMeier regression model was used to analyze the relationship between differential proteins and patients’ prognosis, and to map survival curves.ResultsProteomic analyses revealed that 22 proteins were abnormally expressed (including upregulation in 13 and downregulation in 9) in glioma tissues compared with paraneoplastic tissues. The screened four proteins with the most obviously differential expression were GLUD1, VIM, PRDX1 and MAT1A. The immunohistochemical results showed that expressions of GLUD1 (P=0.006) and PRDX1 (P<0.001) were significantly upregulated in glioma tissues, while that of MAT1A was significantly downregulated (P=0.001), and there was no statistical difference in VIM expression (P=0.118). Correlation analyses showed that the expression level of PRDX1 was significantly correlated with pathological grade of glioma (P=0.008) and patients’ survival (P=0.004), but not with patients’ age, gender and tumor diameter (all P>0.05). There were no significant correlations between the expressions of GLUD1 and MAT1A and patients’ age, gender and survival rate as well as pathological grade and diameter of tumor (all P>0.05). The 3year survival rates of PRDX1 high expression group and low expression group were 27.4% and 57.1%, respectively. And the difference of 3year survival rate between the two groups was statistically significant (P=0.011).ConclusionThe expression of PRDX1 is upregulated in human glioma tissues and significantly associated with pathological grade and poor prognosis of the tumor.

Key words:Glioma|Biomarker|Proteomics|Differential proteins