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.
Bibliographical noteFunding Information:
Funding: This study was kindly funded by the Brain Tumour Research charity, and by a research fellowship awarded to A.S. by the Royal College of Surgeons of England (RCSEng). D.B. was supported in part with a FP7 Marie Curie Actions (PCOFUND-GA-2012-600181) fellowship via The CASCADE International Fellowship Program. The methylation experiments in this study were supported by: Neuroscience, the German Cancer Aid (70112956) and the Else Kröner-Fresenius Stiftung (EKFS 2015_A60). F.S. is a fellow of the Else Kröner Excellence Program of the Else Kröner-Fresenius Stiftung (EKFS 2017_EKES.24).
This study was kindly funded by the Brain Tumour Research charity, and by a research fellowship awarded to A.S. by the Royal College of Surgeons of England (RCSEng). D.B. was supported in part with a FP7 Marie Curie Actions (PCOFUND-GA-2012-600181) fellowship via The CASCADE International Fellowship Program. The methylation experiments in this study were supported by: Neuroscience, the German Cancer Aid (70112956) and the Else Kr?ner-Fresenius Stiftung (EKFS 2015_A60). F.S. is a fellow of the Else Kr?ner Excellence Program of the Else Kr?ner-Fresenius Stiftung (EKFS 2017_EKES.24). We are grateful to all the neurosurgeons, nurses, neuropathology staff and research assistant practitioners at the University Hospitals Plymouth and North Bristol NHS trusts involved in specimen procurement and consenting patients to this study. We thank the Walton Research Tissue bank and the UK Brain Archive Information Network (BRAIN UK) for providing the additional plasma and FFPE samples used in this study. We also thank the Brain Tumour Research charity and the Royal College of Surgeons of England for supporting this work. We acknowledge the advice/input from Sara Ferluga who was involved in the initial planning of the project, and the mass spectrometry service provided by Vikram Sharma.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Aged, 80 and over
- Biomarkers, Tumor/blood
- Calcium-Binding Proteins/blood
- Extracellular Matrix Proteins/blood
- Gene Expression Regulation, Neoplastic/genetics
- Meningeal Neoplasms/blood
- Middle Aged
- Neoplasm Grading