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

International Journal of Molecular Sciences

卷:22

DavidA Hilton¹  Felix Sahm²  Mario Teo³  MichaelD Jenkinson⁴  Daniele Baiz⁵  Sylwia Ammoun⁵  ClaireL Adams⁵  COliver Hanemann⁵  AgbolahanA Sofela⁵  Emanuela Ercolano⁵  KathreenaM Kurian⁶  PeterC Whitfield⁷ 

[1] Cellular and Anatomical Pathology, University Hospitals Plymouth NHS Trust, Derriford Road, Plymouth PL6 8DH, UK;

[2] Department of Neuropathology, Institute of Pathology, University Hospital Heidelberg, 69126 Heidelberg, Germany;

[3] Department of Neurosurgery, Southmead Hospital, Bristol BS10 5NB, UK;

[4] Department of Neurosurgery, The Walton Centre NHS Foundation Trust, Lower Lane, Liverpool L9 7LJ, UK;

[5] 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;

[6] Institute of Clinical Neuroscience, University of Bristol and Southmead Hospital, North Bristol Trust, Bristol BS8 1QU, UK;

[7] South West Neurosurgery Centre, University Hospitals Plymouth NHS Trust, Derriford Road, Plymouth PL6 8DH, UK;

关键词: meningioma;    atypical;    benign;    biomarker;    plasma;   

DOI  :  10.3390/ijms22020560

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown