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Caveolin-1, a key mediator across multiple pathways in glioblastoma and an independent negative biomarker of patient survival

Moriconi, Chiara, Civita, Prospero, Neto, Catia, Pilkington, Geoffrey J. and Gumbleton, Mark 2021. Caveolin-1, a key mediator across multiple pathways in glioblastoma and an independent negative biomarker of patient survival. Frontiers in Oncology 11 , 701933. 10.3389/fonc.2021.701933

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Glioblastoma (GB) remains an aggressive malignancy with an extremely poor prognosis. Discovering new candidate drug targets for GB remains an unmet medical need. Caveolin-1 (Cav-1) has been shown to act variously as both a tumour suppressor and tumour promoter in many cancers. The implications of Cav-1 expression in GB remains poorly understood. Using clinical and genomic databases we examined the relationship between tumour Cav-1 gene expression (including its spatial distribution) and clinical pathological parameters of the GB tumour and survival probability in a TCGA cohort (n=155) and CGGA cohort (n=220) of GB patients. High expression of Cav-1 represented a significant independent predictor of shortened survival (HR = 2.985, 5.1 vs 14.9 months) with a greater statistically significant impact in female patients and in the Proneural and Mesenchymal GB subtypes. High Cav-1 expression correlated with other factors associated with poor prognosis: IDH w/t status, high histological tumour grade and low KPS score. A total of 4879 differentially expressed genes (DEGs) in the GB tumour were found to correlate with Cav-1 expression (either positively or negatively). Pathway enrichment analysis highlighted an over-representation of these DEGs to certain biological pathways. Focusing on those that lie within a framework of epithelial to mesenchymal transition and tumour cell migration and invasion we identified 27 of these DEGs. We then examined the prognostic value of Cav-1 when used in combination with any of these 27 genes and identified a subset of combinations (with Cav-1) indicative of co-operative synergistic mechanisms of action. Overall, the work has confirmed Cav-1 can serve as an independent prognostic marker in GB, but also augment prognosis when used in combination with a panel of biomarkers or clinicopathologic parameters. Moreover, Cav-1 appears to be linked to many signalling entities within the GB tumour and as such this work begins to substantiate Cav-1 or its associated signalling partners as candidate target for GB new drug discovery.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
Publisher: Frontiers Media
ISSN: 2234-943X
Date of First Compliant Deposit: 27 August 2021
Date of Acceptance: 28 July 2021
Last Modified: 04 Aug 2022 01:44

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