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Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482667/ https://www.ncbi.nlm.nih.gov/pubmed/32974197 http://dx.doi.org/10.3389/fonc.2020.01600 |
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author | Mukherjee, Shuvolina Biswas, Deeptarup Gadre, Rucha Jain, Pooja Syed, Nelofer Stylianou, Julianna Zeng, Qingyu Mahadevan, Anita Epari, Sridhar Shetty, Prakash Moiyadi, Aliasgar Roy Ball, Graham Srivastava, Sanjeeva |
author_facet | Mukherjee, Shuvolina Biswas, Deeptarup Gadre, Rucha Jain, Pooja Syed, Nelofer Stylianou, Julianna Zeng, Qingyu Mahadevan, Anita Epari, Sridhar Shetty, Prakash Moiyadi, Aliasgar Roy Ball, Graham Srivastava, Sanjeeva |
author_sort | Mukherjee, Shuvolina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7482667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74826672020-09-23 Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers Mukherjee, Shuvolina Biswas, Deeptarup Gadre, Rucha Jain, Pooja Syed, Nelofer Stylianou, Julianna Zeng, Qingyu Mahadevan, Anita Epari, Sridhar Shetty, Prakash Moiyadi, Aliasgar Roy Ball, Graham Srivastava, Sanjeeva Front Oncol Oncology 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. Frontiers Media S.A. 2020-08-26 /pmc/articles/PMC7482667/ /pubmed/32974197 http://dx.doi.org/10.3389/fonc.2020.01600 Text en Copyright © 2020 Mukherjee, Biswas, Gadre, Jain, Syed, Stylianou, Zeng, Mahadevan, Epari, Shetty, Moiyadi, Roy Ball and Srivastava. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Mukherjee, Shuvolina Biswas, Deeptarup Gadre, Rucha Jain, Pooja Syed, Nelofer Stylianou, Julianna Zeng, Qingyu Mahadevan, Anita Epari, Sridhar Shetty, Prakash Moiyadi, Aliasgar Roy Ball, Graham Srivastava, Sanjeeva Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers |
title | Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers |
title_full | Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers |
title_fullStr | Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers |
title_full_unstemmed | Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers |
title_short | Comprehending Meningioma Signaling Cascades Using Multipronged Proteomics Approaches & Targeted Validation of Potential Markers |
title_sort | comprehending meningioma signaling cascades using multipronged proteomics approaches & targeted validation of potential markers |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482667/ https://www.ncbi.nlm.nih.gov/pubmed/32974197 http://dx.doi.org/10.3389/fonc.2020.01600 |
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