期刊论文详细信息
Frontiers in Oncology
Caveolin-1, a Key Mediator Across Multiple Pathways in Glioblastoma and an Independent Negative Biomarker of Patient Survival
Mark Gumbleton1  Catia Neto1  Geoffrey J. Pilkington2  Prospero Civita2  Chiara Moriconi3 
[1] Biomedical Sciences, University of Portsmouth, Portsmouth, United Kingdom;;Brain Tumour Research Centre, School of Pharmacy &Department of Pathology and Cell Biology, Columbia University, New York Presbyterian Hospital, New York, NY, United States;School of Pharmacy and Pharmaceutical Sciences, College of Biomedical and Life Sciences, Cardiff University, Cardiff, United Kingdom;
关键词: glioblastoma;    caveolin-1;    prognostic;    survival;    gender;    TCGA;   
DOI  :  10.3389/fonc.2021.701933
来源: DOAJ
【 摘 要 】

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.

【 授权许可】

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