Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis
Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis
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ANXA2、PGAM1、CALR表达水平与胶质瘤分级和预后的相关性
DOI：
10.3171/2012.9.jns112134
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发表时间：
2013-04-01
影响因子：
4.1
通讯作者：
Gao, Yilu
中科院分区：
文献类型：
--
作者：
Gao, Huasong;Yu, Bin;Gao, Yilu
Object.神经胶质瘤的诊断和预后的生物标志物缺乏。为了阐明新的诊断和预后靶点，使用常规方法来评估正常细胞和肿瘤细胞的蛋白质谱之间的差异。本研究的目的是探讨新的差异表达蛋白及其在胶质瘤中的作用。使用2D聚丙烯酰胺凝胶电泳使用C6胶质瘤细胞和大鼠星形胶质细胞的蛋白质谱的差异进行了比较。分析ANXA 2、PGAM 1和CALR在胶质瘤组织和正常脑组织中的mRNA和蛋白表达。使用短干扰RNA双链体中断U87胶质瘤细胞系中ANXA 2的表达，并评估ANXA 2在胶质瘤细胞的迁移和侵袭中的作用。采用免疫组化方法检测130例脑胶质瘤标本中ANXA 2、PGAM 1和CALR的表达，并采用Kaplan-Meier和考克斯回归分析评估其在脑胶质瘤预后中的作用。ANXA 2和PGAM 1的表达水平在胶质瘤样品中显著高于正常脑样品，而CALR的表达水平则显著低于正常脑样品。ANXA 2、PGAM 1和CALR表达与胶质瘤患者的分级和生存相关。多因素分析进一步显示ANXA 2是胶质瘤的独立预后标志物。在使用短干扰RNA抑制ANXA 2表达后，U87细胞的体外迁移和侵袭能力降低。ANXA 2、PGAM 1和CALR的蛋白表达改变在胶质瘤中被发现，ANXA 2提供了一种新的预后价值。(http/thejns.org/doi/abs/10.3171/2012.9.JNS112134）
Object. Biomarkers for the diagnosis and prognosis of gliomas are lacking. To elucidate new diagnostic and prognostic targets, a routine method is used to evaluate differences between the protein profile of normal and tumor cells. The object of the current study was to investigate novel differentially expressed proteins and their roles in gliomas.Methods. Differences in the protein profile were compared using 2D polyacrylamide gel electrophoresis using C6 glioma cells and rat astrocytes. The mRNA and protein expression of ANXA2, PGAM1, and CALR were analyzed in glioma tissues and normal brain tissues. The expression of ANXA2 in the U87 glioma cell line was interrupted using short interfering RNA duplexes, and the role of ANXA2 in the migration and invasiveness of glioma cells was assessed. The expression of ANXA2, PGAM1, and CALR was examined further by immunohistochemical analysis using 130 glioma samples obtained in patients, and their prognostic roles in gliomas were evaluated using Kaplan-Meier and Cox regression analyses.Results. Significantly higher expression levels of ANXA2 and PGAM1 and a lower level of CALR were found in glioma samples than in the normal brain samples. ANXA2, PGAM1, and CALR expression correlated with the grade and survival of patients with gliomas. Multivariate analysis further revealed that ANXA2 was an independent prognostic marker for glioma. After ANXA2 expression was suppressed using short interfering RNA, U87 cells had decreased migratory and invasive capabilities in vitro.Conclusions. Protein expression alterations in ANXA2, PGAM1, and CALR were found in gliomas, and ANXA2 provided a novel prognostic value. (http/thejns.org/doi/abs/10.3171/2012.9.JNS112134)