Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Global & targeted proteomics reveal major dysregulated networks in meningiomas (#739)

Shuvolina Mukherjee 1 , Sanjeeva Srivastava 1 , Deeptarup Biswas 1 , Rucha Gadre 1 , Pooja Jain 2 , Nelofer Syed 3 , Tzouliana Stylianou 3 , Graham Ball 4 , Epari Sridhar 5 , Aliasgar Moiyadi 6 , Prakash Shetty 6
  1. Indian Institute of Technology (IIT) Bombay, Mumbai, MAHARASHTRA, India
  2. Centre for Integrative Systems Biology and Bioinformatics (CISBIO), Imperial College, London, Uk
  3. Division of Brain Sciences, Department of Medicine, Imperial College, London, UK
  4. School of Science and technology, Nottingham Trent University, Nottingham, UK
  5. Department of Pathology, Tata Memorial Center, Mumbai, Maharashtra, India
  6. Department of Neurosurgery, Tata Memorial Center, Mumbai, Maharashtra, India
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.