Faculty of Health, Medicine, Dentistry and Human Sciences, The Institute of Translational and Stratified Medicine, University of Plymouth, The John Bull Building, Plymouth Science Park, Research Way, Plymouth PL6 8BU, UK.
South West Neurosurgery Centre, University Hospitals Plymouth NHS Trust, Derriford Road, Plymouth PL6 8DH, UK.
Int J Mol Sci. 2021 Jan 8;22(2):560. doi: 10.3390/ijms22020560.
There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas. There is currently no consensus on the optimum management of WHO grade II meningiomas. In this study, we identified the calcium binding extracellular matrix glycoprotein, Fibulin-2, via mass-spectrometry-based proteomics, assessed its expression in grade I and II meningiomas and explored its potential as a grade II biomarker. A total of 87 grade I and 91 grade II different meningioma cells, tissue and plasma samples were used for the various experimental techniques employed to assess Fibulin-2 expression. The tumours were reviewed and classified according to the 2016 edition of the Classification of the Tumours of the central nervous system (CNS). Mass spectrometry proteomic analysis identified Fibulin-2 as a differentially expressed protein between grade I and II meningioma cell cultures. Fibulin-2 levels were further evaluated in meningioma cells using Western blotting and Real-time Quantitative Polymerase Chain Reaction (RT-qPCR); in meningioma tissues via immunohistochemistry and RT-qPCR; and in plasma via Enzyme-Linked Immunosorbent Assay (ELISA). Proteomic analyses ( < 0.05), Western blotting ( < 0.05) and RT-qPCR ( < 0.01) confirmed significantly higher Fibulin-2 (FBLN2) expression levels in grade II meningiomas compared to grade I. Fibulin-2 blood plasma levels were also significantly higher in grade II meningioma patients compared to grade I patients. This study suggests that elevated Fibulin-2 might be a novel grade II meningioma biomarker, when differentiating them from the grade I tumours. The trend of Fibulin-2 expression observed in plasma may serve as a useful non-invasive biomarker.
目前，人们迫切需要寻找生物标志物，以帮助诊断、临床管理、预测和随访脑膜瘤。对于世界卫生组织（WHO）分级 II 型脑膜瘤，目前尚无最佳的治疗共识。在这项研究中，我们通过基于质谱的蛋白质组学方法鉴定了钙结合细胞外基质糖蛋白纤维连接蛋白-2（Fibulin-2），评估了其在 I 级和 II 级脑膜瘤中的表达，并探讨了其作为 II 级生物标志物的潜力。总共使用了 87 个 I 级和 91 个 II 级不同的脑膜瘤细胞、组织和血浆样本，用于评估 Fibulin-2 表达的各种实验技术。肿瘤根据 2016 年版中枢神经系统肿瘤分类（CNS）进行回顾和分类。质谱蛋白质组学分析鉴定出 Fibulin-2 是 I 级和 II 级脑膜瘤细胞培养物中差异表达的蛋白质。使用 Western blot 和实时定量聚合酶链反应（RT-qPCR）进一步评估脑膜瘤细胞中的 Fibulin-2 水平；通过免疫组织化学和 RT-qPCR 评估脑膜瘤组织中的 Fibulin-2 水平；通过酶联免疫吸附试验（ELISA）评估血浆中的 Fibulin-2 水平。蛋白质组学分析（<0.05）、Western blot（<0.05）和 RT-qPCR（<0.01）均证实，与 I 级脑膜瘤相比，II 级脑膜瘤的 Fibulin-2（FBLN2）表达水平显著升高。与 I 级脑膜瘤患者相比，II 级脑膜瘤患者的 Fibulin-2 血浆水平也显著升高。本研究表明，在区分 I 级和 II 级脑膜瘤时，Fibulin-2 的升高可能是一种新的 II 级脑膜瘤生物标志物。在血浆中观察到的 Fibulin-2 表达趋势可能是一种有用的非侵入性生物标志物。
