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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.
AuthorsAgbolahan 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
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 2 (Jan 08 2021) ISSN: 1422-0067 [Electronic] Switzerland
PMID33429944 (Publication Type: Journal Article)
Chemical References
  • Biomarkers, Tumor
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • fibulin 2
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (blood)
  • Calcium-Binding Proteins (blood)
  • Extracellular Matrix Proteins (blood)
  • Female
  • Gene Expression Regulation, Neoplastic (genetics)
  • Humans
  • Male
  • Meningeal Neoplasms (blood, genetics, pathology)
  • Meningioma (blood, genetics, pathology)
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Proteomics

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