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Open AccessArticle

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

1
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
2
South West Neurosurgery Centre, University Hospitals Plymouth NHS Trust, Derriford Road, Plymouth PL6 8DH, UK
3
Cellular and Anatomical Pathology, University Hospitals Plymouth NHS Trust, Derriford Road, Plymouth PL6 8DH, UK
4
Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Lower Lane, Liverpool L9 7LJ, UK
5
Institute of Translational Medicine and School of Medicine, University of Liverpool, Liverpool L69 3GE, UK
6
Institute of Clinical Neuroscience, University of Bristol and Southmead Hospital, North Bristol Trust, Bristol BS8 1QU, UK
7
Department of Neurosurgery, Southmead Hospital, Bristol BS10 5NB, UK
8
Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, 69126 Heidelberg, Germany
9
Clinical Cooperation Unit Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ), 69126 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 560; https://doi.org/10.3390/ijms22020560
Received: 12 December 2020 / Revised: 4 January 2021 / Accepted: 5 January 2021 / Published: 8 January 2021
(This article belongs to the Special Issue Biomarkers for Meningioma)
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. View Full-Text
Keywords: meningioma; atypical; benign; biomarker; plasma meningioma; atypical; benign; biomarker; plasma
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MDPI and ACS Style

Sofela, A.A.; Hilton, D.A.; Ammoun, S.; Baiz, D.; Adams, C.L.; Ercolano, E.; Jenkinson, M.D.; Kurian, K.M.; Teo, M.; Whitfield, P.C.; Sahm, F.; Hanemann, C.O. Fibulin-2: A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas. Int. J. Mol. Sci. 2021, 22, 560. https://doi.org/10.3390/ijms22020560

AMA Style

Sofela AA, Hilton DA, Ammoun S, Baiz D, Adams CL, Ercolano E, Jenkinson MD, Kurian KM, Teo M, Whitfield PC, Sahm F, Hanemann CO. Fibulin-2: A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas. International Journal of Molecular Sciences. 2021; 22(2):560. https://doi.org/10.3390/ijms22020560

Chicago/Turabian Style

Sofela, Agbolahan A.; Hilton, David A.; Ammoun, Sylwia; Baiz, Daniele; Adams, Claire L.; Ercolano, Emanuela; Jenkinson, Michael D.; Kurian, Kathreena M.; Teo, Mario; Whitfield, Peter C.; Sahm, Felix; Hanemann, C. O. 2021. "Fibulin-2: A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas" Int. J. Mol. Sci. 22, no. 2: 560. https://doi.org/10.3390/ijms22020560

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