Introduction: Meningiomas are tumors originating from the outer layering of the brain and comprise of nearly 30% of CNS tumors of the brain. In certain cases, the tumor location is unamenable for complete resection leading to comorbidities; however, there are very limited effective therapeutic strategies. The current study investigates the patient specific global proteome of meningiomas resulting in identification of 4639 proteins (1% FDR, ≥ 2 unique peptides) Investigation of proteomic alterations that corroborate with radiology and histopathology was also done. An in-depth analysis revealed upheaval of Focal adhesion, PI3-Akt pathways which were further probed using inhibitor against Integrin Linked Kinase, a major influencer for the key pathways.
Materials & Methods: The study comprised of tissue extraction from surgically resected biospecimens of meningiomas. LC MS/MS analysis was performed using LFQ approach using Q-Exactive platform (Thermo Fisher Scientific) & Proteome Discoverer 2.2 was used for data analysis. In silico analysis was done using GO term-based enrichments & Machine learning approaches
Conclusion: We have identified candidates that are differentially abundant based on the radiological location of the tumor like FBLN5 and NUP210. IHC-based WHO grade analysis suggested potentially new subtype in meningioma Grade-I. Additionally, in silico analysis points out prominent alterations in Focal Adhesion & NF kappa B pathways in meningioma patients. We observed perturbations in several of the pathway components via Global proteomic profiling in treated meningioma cell line (Ben-Men1) which substantiates potential of ILK inhibition as a therapeutic adjunct for recurrent and non-resectable meningioma cases.