Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma.
Cells
; 12(20)2023 10 18.
Article
en En
| MEDLINE
| ID: mdl-37887327
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Meníngeas
/
Meningioma
Tipo de estudio:
Systematic_reviews
Límite:
Humans
Idioma:
En
Revista:
Cells
Año:
2023
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Suiza