Expression of GLUT1 in Pseudopalisaded and Perivascular Tumor Cells Is an Independent Prognostic Factor for Patients With Glioblastomas

Expression of GLUT1 in Pseudopalisaded and Perivascular Tumor Cells Is an Independent Prognostic Factor for Patients With Glioblastomas
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DOI:
10.1093/jnen/nly124
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发表时间:
2019-05-01
影响因子:
3.2
通讯作者:
Morioka, Motohiro
Morioka, Motohiro
中科院分区:
医学4区
文献类型:
--
作者:
Komaki, Satoru;Sugita, Yasuo;Morioka, Motohiro

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胶质母细胞瘤是高度侵袭性的脑肿瘤,预后特别差。葡萄糖转运蛋白-1(GLUT 1/SLC 2A 1)是一种在多种肿瘤中表达的单向转运蛋白,可能与恶性肿瘤糖代谢有关,也可能与胶质母细胞瘤的预后有关。GLUT 1是中枢神经系统糖代谢所必需的。为了阐明GLUT 1在胶质母细胞瘤中的确切作用,我们通过免疫组织化学和原位RNA杂交评估了GLUT 1在患者样本中的表达和定位。结果表明GLUT 1主要表达于血管周围和假阳性的肿瘤细胞膜上。所有样本均在一定程度上表达GLUT 1,其中30.8%显示出较强的染色。根据这些数据,将样本分为高表达组和低表达组,尽管GLUT 1高表达组中SLC 2A 1 mRNA表达也较高。Kaplan-Meier生存曲线显示,高GLUT 1表达与较低的总生存率(对数秩检验,p = 0.001)和较差的患者生存率(p = 0.001)相关。最后,MIB-1染色在高GLUT 1表达样本中更强(p = 0.0004),表明与增殖有关。因此,我们假设GLUT 1在胶质母细胞瘤中的表达可能会增强糖酵解,影响患者的预后。在胶质母细胞瘤患者中检查GLUT 1可能为改善预后提供一种新的预后工具。
Glioblastomas are highly aggressive brain tumors with a particularly poor prognosis. Glucose transporter-1 (GLUT1/SLC2A1), a uniporter that is expressed by various carcinomas and may be involved in malignant neoplasm glycometabolism, may also be related to prognosis in glioblastomas. GLUT1 is essential to central nervous system glycometabolism. To clarify the exact role of GLUT1 in glioblastoma, we assessed the expression and localization of GLUT1 in patient samples by immunohistochemistry and in situ RNA hybridization. This revealed that GLUT1 was mainly expressed on perivascular and pseudopalisaded tumor cell membranes. All samples expressed GLUT1 to some degree, with 30.8% showing stronger staining. On the basis of these data, samples were divided into high and low expression groups, although SLC2A1 mRNA expression was also higher in the high GLUT1 expression group. Kaplan-Meier survival curves revealed that high GLUT1 expression associated with lower overall survival (log-rank test, p = 0.001) and worse patient prognoses (p = 0.001). Finally, MIB-1 staining was stronger in high GLUT1 expression samples (p = 0.0004), suggesting a link with proliferation. We therefore hypothesize that GLUT1 expression in glioblastomas may enhance glycolysis, affecting patient prognosis. Examination of GLUT1 in patients with glioblastomas may provide a new prognostic tool to improve outcome.