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Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma

Meningioma, a primary brain tumor, is commonly encountered and accounts for 39% of overall CNS tumors. Despite significant progress in clinical research, conventional surgical and clinical interventions remain the primary treatment options for meningioma. Several proteomics and transcriptomics studi...

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Autores principales: Biswas, Deeptarup, Halder, Ankit, Barpanda, Abhilash, Ghosh, Susmita, Chauhan, Aparna, Bhat, Lipika, Epari, Sridhar, Shetty, Prakash, Moiyadi, Aliasgar, Ball, Graham Roy, Srivastava, Sanjeeva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604908/
https://www.ncbi.nlm.nih.gov/pubmed/37887327
http://dx.doi.org/10.3390/cells12202483
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author Biswas, Deeptarup
Halder, Ankit
Barpanda, Abhilash
Ghosh, Susmita
Chauhan, Aparna
Bhat, Lipika
Epari, Sridhar
Shetty, Prakash
Moiyadi, Aliasgar
Ball, Graham Roy
Srivastava, Sanjeeva
author_facet Biswas, Deeptarup
Halder, Ankit
Barpanda, Abhilash
Ghosh, Susmita
Chauhan, Aparna
Bhat, Lipika
Epari, Sridhar
Shetty, Prakash
Moiyadi, Aliasgar
Ball, Graham Roy
Srivastava, Sanjeeva
author_sort Biswas, Deeptarup
collection PubMed
description Meningioma, a primary brain tumor, is commonly encountered and accounts for 39% of overall CNS tumors. Despite significant progress in clinical research, conventional surgical and clinical interventions remain the primary treatment options for meningioma. Several proteomics and transcriptomics studies have identified potential markers and altered biological pathways; however, comprehensive exploration and data integration can help to achieve an in-depth understanding of the altered pathobiology. This study applied integrated meta-analysis strategies to proteomic and transcriptomic datasets comprising 48 tissue samples, identifying around 1832 common genes/proteins to explore the underlying mechanism in high-grade meningioma tumorigenesis. The in silico pathway analysis indicated the roles of extracellular matrix organization (EMO) and integrin binding cascades in regulating the apoptosis, angiogenesis, and proliferation responsible for the pathobiology. Subsequently, the expression of pathway components was validated in an independent cohort of 32 fresh frozen tissue samples using multiple reaction monitoring (MRM), confirming their expression in high-grade meningioma. Furthermore, proteome-level changes in EMO and integrin cell surface interactions were investigated in a high-grade meningioma (IOMM-Lee) cell line by inhibiting integrin-linked kinase (ILK). Inhibition of ILK by administrating Cpd22 demonstrated an anti-proliferative effect, inducing apoptosis and downregulating proteins associated with proliferation and metastasis, which provides mechanistic insight into the disease pathophysiology.
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spelling pubmed-106049082023-10-28 Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma Biswas, Deeptarup Halder, Ankit Barpanda, Abhilash Ghosh, Susmita Chauhan, Aparna Bhat, Lipika Epari, Sridhar Shetty, Prakash Moiyadi, Aliasgar Ball, Graham Roy Srivastava, Sanjeeva Cells Article Meningioma, a primary brain tumor, is commonly encountered and accounts for 39% of overall CNS tumors. Despite significant progress in clinical research, conventional surgical and clinical interventions remain the primary treatment options for meningioma. Several proteomics and transcriptomics studies have identified potential markers and altered biological pathways; however, comprehensive exploration and data integration can help to achieve an in-depth understanding of the altered pathobiology. This study applied integrated meta-analysis strategies to proteomic and transcriptomic datasets comprising 48 tissue samples, identifying around 1832 common genes/proteins to explore the underlying mechanism in high-grade meningioma tumorigenesis. The in silico pathway analysis indicated the roles of extracellular matrix organization (EMO) and integrin binding cascades in regulating the apoptosis, angiogenesis, and proliferation responsible for the pathobiology. Subsequently, the expression of pathway components was validated in an independent cohort of 32 fresh frozen tissue samples using multiple reaction monitoring (MRM), confirming their expression in high-grade meningioma. Furthermore, proteome-level changes in EMO and integrin cell surface interactions were investigated in a high-grade meningioma (IOMM-Lee) cell line by inhibiting integrin-linked kinase (ILK). Inhibition of ILK by administrating Cpd22 demonstrated an anti-proliferative effect, inducing apoptosis and downregulating proteins associated with proliferation and metastasis, which provides mechanistic insight into the disease pathophysiology. MDPI 2023-10-18 /pmc/articles/PMC10604908/ /pubmed/37887327 http://dx.doi.org/10.3390/cells12202483 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Biswas, Deeptarup
Halder, Ankit
Barpanda, Abhilash
Ghosh, Susmita
Chauhan, Aparna
Bhat, Lipika
Epari, Sridhar
Shetty, Prakash
Moiyadi, Aliasgar
Ball, Graham Roy
Srivastava, Sanjeeva
Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma
title Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma
title_full Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma
title_fullStr Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma
title_full_unstemmed Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma
title_short Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma
title_sort integrated meta-omics analysis unveils the pathways modulating tumorigenesis and proliferation in high-grade meningioma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10604908/
https://www.ncbi.nlm.nih.gov/pubmed/37887327
http://dx.doi.org/10.3390/cells12202483
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