Progranulin overexpression predicts overall survival in patients with glioblastoma
Progranulin overexpression predicts overall survival in patients with glioblastoma
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颗粒体蛋白前体过度表达可预测胶质母细胞瘤患者的总生存期
DOI：
10.1007/s12032-011-0131-6
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发表时间：
2012-12-01
期刊：
影响因子：
3.4
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Wang, Minqing;Li, Gang;Zhang, Jian
尽管多模式治疗，星形细胞瘤患者仍然面临生存率低，识别有价值的预后因素是至关重要的，以产生有效的个体化治疗策略。本研究的目的是研究颗粒蛋白前体（PGRN）在星形细胞瘤中的表达，并通过对肿瘤细胞和血管的PGRN免疫反应性进行评分，探讨其与肿瘤分级和患者总生存率的关系。应用免疫组织化学方法对210例不同WHO分级的星形细胞瘤和14例正常脑组织中PGRN进行了研究。用半定量RT-PCR和Western blot检测35例肿瘤组织中的表达。采用酶免疫分析法检测胶质母细胞瘤患者血清PGRN水平。PGRN在正常脑组织中几乎检测不到表达，但在星形细胞瘤细胞和肿瘤血管中的表达随着病理分级而增加。胶质母细胞瘤患者血清中TNF-α水平明显高于健康对照组。在II级星形细胞瘤中，血管PGRN强表达与肿瘤复发密切相关。在胶质母细胞瘤中，高的总PGRN表达、强的血管PGRN表达和强的肿瘤细胞PGRN表达在单变量分析中均与患者存活率降低相关。然而，在多变量分析中，只有总PGRN表达以及血管PGRN表达状态与患者的生存独立相关。这些结果表明，PGRN，参与星形细胞瘤的进展，可能作为胶质母细胞瘤的预后生物标志物。
Despite multimodal treatment, patients with astrocytoma still face a poor survival, and identification of valuable prognostic factors is crucial to yield effective individual therapy strategies. The aim of this study was to investigate progranulin (PGRN) expression in astrocytomas and explore its association with tumor grade and overall patient survival by scoring the PGRN immunoreactivity of both tumor cells and blood vessels. About 210 astrocytoma samples with different WHO grades and 14 normal brain tissues were studied by immunohistochemistry for PGRN. Semi-quantitative RT-PCR and Western blot were carried out to confirm its expression in 35 tumor specimens. Serum levels of PGRN in glioblastoma were examined by enzyme immunometric assay. PGRN expression was almost undetectable in the normal brain tissues by immunohistochemistry but increased in both astrocytoma cells and tumor blood vessels with pathological grading. Sera in glioblastoma were significantly higher than in healthy control. In grade II astrocytoma, strong vascular PGRN expression was closely related to tumor recurrence. In glioblastoma, high total PGRN expression, strong vascular PGRN expression, and strong tumor cellular PGRN expression all correlated with decreased patient survival in univariate analysis. However, only total PGRN expression as well as vascular PGRN expression status was independently associated with patient's survival in the multivariate analysis. These results suggest that PGRN, involved in astrocytoma progression, may serve as a prognostic biomarker for glioblastoma.