Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Neuropathol Exp Neurol. 2020 May 1;79(5):493-499. doi: 10.1093/jnen/nlaa013.
Although the microtubule-associated protein tau is well studied in human neurodegeneration, the role of tau in neoplastic brain diseases is not well understood. Recently, studies have shown tau mRNA expression is associated with improved survival in human infiltrating gliomas. However, the biologic basis of this association is largely unexplored. Using 2 independent publicly available mRNA databases, we show that high tau mRNA expression is associated with improved patient survival in infiltrating gliomas. Higher tau protein expression is also associated with improved patient prognosis in infiltrating gliomas by immunohistochemical staining of tissue microarrays. This prognostic association is in part due to higher tau mRNA and protein expression in IDH-mutant infiltrating astrocytomas. Expression of tau in an IDH-wildtype glioblastoma cell line selectively impairs cell migration in assays designed to mimic tumor invasion. These findings suggest that tau expression is not only associated with IDH mutation status but also may contribute to improved patient outcomes by impairing tumor invasion.
尽管微管相关蛋白 tau 在人类神经退行性疾病中得到了很好的研究,但 tau 在肿瘤性脑疾病中的作用还不是很清楚。最近的研究表明,tau mRNA 的表达与人类浸润性神经胶质瘤患者的生存改善有关。然而,这种关联的生物学基础在很大程度上还没有被探索。我们使用 2 个独立的公开 mRNA 数据库,显示在浸润性神经胶质瘤中,tau mRNA 表达水平较高与患者生存改善有关。通过对组织微阵列进行免疫组织化学染色,tau 蛋白的高表达也与浸润性神经胶质瘤患者的预后改善有关。这种预后关联部分是由于 IDH 突变浸润性星形细胞瘤中 tau mRNA 和蛋白表达水平较高所致。在设计用于模拟肿瘤侵袭的实验中,IDH 野生型神经胶质母细胞瘤细胞系中 tau 的表达选择性地损害了细胞迁移。这些发现表明,tau 的表达不仅与 IDH 突变状态有关,而且可能通过损害肿瘤侵袭来改善患者的预后。