Identifying novel molecular differences between WHO grade I and II meningiomas

Abstract

Abstract Background With the increasing emphases on the integrated histo-pheno-genotypical diagnoses of central nervous system (CNS) tumours, there is a pressing need for the identification of biomarkers to aid in the clinical management, diagnosis, prognosis and follow-up of meningiomas too. WHO grade II meningiomas remain a very controversial group of CNS tumours to diagnose/treat, compared to the more prevalent and extensively researched grade I tumours. Typical clinical scenarios include; the serum diagnosis of conservatively managed tumours, follow-up of surgically managed patients and prognostication, for predicting grade progression. We herein describe the identification of novel biomolecular differences between grade I and II meningiomas. Aim To identify biomarkers unique to grade II meningiomas (versus grade I) and describe their potential use in typical clinical scenarios. Methods Unbiased global proteomic analyses of four grade I & II primary-meningioma cells were carried out to identify proteins differentially expressed between both grades. Differential expression and statistical analyses were performed using Perseus and Microsoft Excel. The significantly differentially expressed proteins were validated by Western blot, IHC and ELISA, using tumour tissue and primary cells. Results We identified 3553 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 most promising candidates have confirmed these patterns of expressions between the two tumour grades. Conclusion There is a need for the identification of grade II biomarkers. The initial findings of this study have identified novel biomolecular differences between grade I/II meningiomas that can potentially aid in the aforementioned typical clinical scenarios.