International Journal of Molecular Sciences (Jan 2021)

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

  • Agbolahan A. Sofela,
  • David A. Hilton,
  • Sylwia Ammoun,
  • Daniele Baiz,
  • Claire L. Adams,
  • Emanuela Ercolano,
  • Michael D. Jenkinson,
  • Kathreena M. Kurian,
  • Mario Teo,
  • Peter C. Whitfield,
  • Felix Sahm,
  • C. Oliver Hanemann

DOI
https://doi.org/10.3390/ijms22020560
Journal volume & issue
Vol. 22, no. 2
p. 560

Abstract

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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 p 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.

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