Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers

Abstract

Meningiomas are one of the most prevalent primary brain tumors. Our study aims to obtain mechanistic insights of meningioma pathobiology using mass spectrometry-based label-free quantitative proteome analysis to identifying druggable targets and perturbed pathways for therapeutic intervention. Label-free based proteomics study was done from peptide samples of 21 patients and 8 non-tumor controls which were followed up with Phosphoproteomics to identify the kinases and phosphorylated components of the perturbed pathways. In silico approaches revealed perturbations in extracellular matrix remodeling and associated cascades. To assess the extent of influence of Integrin and PI3K-Akt pathways, we used an Integrin Linked Kinase inhibitor on patient-derived meningioma cell line and performed a transcriptomic analysis of the components. Furthermore, we designed a Targeted proteomics assay which to the best of our knowledge for very first-time enables identification of peptides from 54 meningioma patients via SRM assay to validate the key proteins emerging from our study. This resulted in the identification of peptides from CLIC1, ES8L2, and AHNK many of which are receptors and kinases and are difficult to be characterized using conventional approaches. Furthermore, we were also able to monitor transitions for proteins like NEK9 and CKAP4 which have been reported to be associated with meningioma pathobiology. We believe, this study can aid in designing peptide-based validation assays for meningioma patients as well as IHC studies for clinical applications.

Multiple Reaction Monitoring-Based Targeted Assays for the Validation of Protein Biomarkers in Brain Tumors

“…The Human Protein Atlas reports a higher expression of VIM in Gliomas (35,36). Mukherjee et al validated the expression of VIM in Meningiomas using MRM (37). In the current study, we have reported four peptides for VIM, not reported elsewhere further strengthening the claim for its use as a biomarker for meningiomas as reported by Mukherjee et al In Meningiomas, the protein CLU was found to be upregulated when compared to controls.…”

Lipid remodeling by hypoxia aggravates migratory potential in pancreatic cancer while maintaining membrane homeostasis

“…The raw data sets were processed using proteome discoverer (PD; version 2.4. Using the parameters discussed in a previous study [23]. In brief, the variable modification of carbamidomethyl and oxidation was set as static modification.…”

Proteome of human glioblastoma and meningioma tissue small extracellular vesicles

“…We identified 75 proteins that were significantly up-regulated in GBM EVs and 40 proteins that were significantly upregulated in MNG EVs ( Figure 6B Supplementary Table 15 ). Proteins that were up regulated in GBM EVs include GFAP, FSCN1, MYO5A, RCN1 and in MNG include MVP (39), DSP (40), and CKAP4 and AHNAK, which have been associated with particular grades of MNG (41, 42) ( Supplementary Table 15 ).…”