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dc.contributor.supervisorHanemann, C. Oliver
dc.contributor.authorSofela, Agbolahan
dc.contributor.otherFaculty of Healthen_US
dc.date.accessioned2021-05-24T08:50:41Z
dc.date.issued2021
dc.identifier10605298en_US
dc.identifier.urihttp://hdl.handle.net/10026.1/17201
dc.description.abstract

Background: There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas, facilitated by recent advances in meningioma genomics. WHO grade II meningiomas remain a controversial group of CNS tumours to diagnose/treat, compared to the more prevalent and extensively researched grade I tumours. Aim: To identify molecular signatures (biomarkers) unique to grade II meningiomas (versus grade I). Methods: I combined literature review with an unbiased global proteomic analysis of four grade I and four grade II primary (meningioma) cell cultures, to identify proteins differentially expressed between both grades. Validation of the significantly differentially expressed proteins was then performed by Western blotting (WB) and quantitative polymerase chain reaction (qPCR) in primary cells; via WB, immunohistochemistry and qPCR in tissue; and in plasma, via enzyme-linked immunosorbent assay (ELISA). Results: I identified 3554 proteins commonly expressed in both meningioma grades. Further analysis revealed that 86 of these were significantly-differentially up/down-regulated. Initial validation studies on some of the promising candidates have confirmed the patterns of expression between the two tumour grades. Of these 86, we discovered that the calcium binding extracellular matrix glycoprotein, Fibulin-2 was significantly differentially expressed between grade I and II meningiomas, at protein and gene expression levels. Proteomic analyses (p<0.05), Western blotting (p<0.01) and qPCR (p<0.01) confirmed significantly higher Fibulin-2 expression levels in grade II meningiomas compared to grade I. To distinguish between grade I and II meningiomas, Receiver Operating Characteristic (ROC) analysis of Fibulin-2 qPCR expression levels in meningioma tissue indicated an AUC of 0.73 (96% specificity). Fibulin-2 blood plasma levels were also significantly higher in grade II meningioma patients compared to grade I patients (cut-off value >2.5ng/ml with 95% specificity). Conclusion: The findings of this study have identified novel biomolecular differences between grade I/II meningiomas that can potentially aid in the diagnosis and clinical management of grade II meningiomas. Elevated Fibulin- 2 levels is proposed as 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.

en_US
dc.description.sponsorshipRoyal College of Surgeons of Englanden_US
dc.description.sponsorshipBrain Tumour Researchen_US
dc.language.isoen
dc.publisherUniversity of Plymouth
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectMeningiomaen_US
dc.subjectAtypicalen_US
dc.subjectBenignen_US
dc.subjectBiomarkeren_US
dc.subjectPlasmaen_US
dc.subjectBlooden_US
dc.subjectImagingen_US
dc.subjectImmunohistochemistryen_US
dc.subjectMass Spectrometryen_US
dc.subjectELISAen_US
dc.subjectqPCRen_US
dc.subjectWestern Blottingen_US
dc.subject.classificationPhDen_US
dc.titleThe identification of biomarker differences between grade I and II meningiomas: Fibulin-2 is a novel biomarker for differentiating grade II from grade I meningiomasen_US
dc.typeThesis
plymouth.versionpublishableen_US
dc.identifier.doihttp://dx.doi.org/10.24382/1176
dc.rights.embargodate2021-11-24T08:50:41Z
dc.rights.embargoperiod6 monthsen_US
dc.type.qualificationDoctorateen_US
rioxxterms.versionNA
plymouth.orcid_idhttps://orcid.org/0000-0002-1101-9896en_US


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