Fibulin-2: A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas

Abstract

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 (p < 0.05), Western blotting (p < 0.05) and RT-qPCR (p < 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.

Tumor Microenvironment and Immune Escape in the Time Course of Glioblastoma

“…The measured changes of TN-C expression did not affect fibulin-2 levels, that are maintained constitutively high in this pathological model. Fibulin-2 has an emergent role in carcinogenesis and high-grade gliomas [ 35 ] and has been recently proposed as a prognostic biomarker for meningiomas [ 36 ]. However, while we observed an increase of fibulin-2 expression in GL261 tumor-bearing mice as compared to sham, fibulin-2 transcriptional expression is frequently downregulated in human glioblastoma (Supplementary Fig.…”

Updated Systematic Review on the Role of Brain Invasion in Intracranial Meningiomas: What, When, Why?

“…This method aims to characterize the entire “protein kit” contained in a cell at a given time and to identify from body fluids analysis possible biomarkers of great functional importance; in some cases, these proteins can be represented by products secreted by pathological cells, affected by a disease. In the neuro-oncological field, proteogenomic characterization has reinforced the robustness of the newly defined molecular groups of brain tumors and uncovered highly abundant and group-specific protein targets in meningioma [ 49 , 50 , 51 , 52 ].…”

Biomarkers for differentiating grade II meningiomas from grade I: a systematic review

“…We recently published data on Fibulin-2, the calcium binding extracellular matrix glycoprotein, as a novel biomarker difference between grade I and II meningiomas. Plasma Fibulin-2 levels were shown to be significantly higher in grade II (n=47) compared to grade I (n=40) meningioma patients, with a Fibulin-2 plasma concentration cut off value > 2.5ng/ml being 95% specific for identifying patients with grade II meningiomas over those with grade I tumours (Sofela et al 2021). This study also confirmed that the trend of grade II meningioma Fibulin-2 over-expression observed is similar at both the protein and RNA levels and can serve as a non-invasive biomarker for predicting (pre-operative) grade and prognosticating likely clinically aggressive (histologically confirmed) grade I meningiomas (Sofela et al 2021).…”