Abstract
Glioblastoma is a highly aggressive disease with poor survival outcomes. An emerging body of literature links the role of the renin-angiotensin system (RAS), well-known for its function in the cardiovascular system, to the progression of cancers. We studied the expression of RAS-related genes (,,,,, and) in The Cancer Genome Atlas (TCGA) glioblastoma cohort, their relationship to patient survival, and association with tumour microenvironment pathways. The expression of RAS genes was then examined in 12 patient-derived glioblastoma cell lines treated with chemoradiation. In cases of glioblastoma within the TCGA,,,, andhad consistent expressions across samples, whileandwere lowly expressed. High expression ofwas independently associated with lower progression-free survival (PFS) (= 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis (= 0.095). The combined expression of RAS receptors (,, and) was positively associated with gene pathways involved in hypoxia, microvasculature, stem cell plasticity, and the molecular characterisation of glioblastoma subtypes. In patient-derived glioblastoma cell lines,andwere upregulated after chemoradiotherapy and correlated with an increase inexpression. This data suggests the RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes.
Overview
- The study investigates the role of the renin-angiotensin system (RAS) in the progression of glioblastoma, a highly aggressive disease with poor survival outcomes. The study uses data from The Cancer Genome Atlas (TCGA) glioblastoma cohort to examine the expression of RAS-related genes (,,,,, and) and their relationship to patient survival and association with tumour microenvironment pathways. The study also examines the expression of RAS genes in 12 patient-derived glioblastoma cell lines treated with chemoradiation. The primary objective of the study is to understand the correlation between RAS and glioblastoma survival outcomes and the changes in the tumour microenvironment associated with RAS activation.
Comparative Analysis & Findings
- The study found that high expression of the RAS gene was independently associated with lower progression-free survival (PFS) (= 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis (= 0.095). The combined expression of RAS receptors (,,,, and) was positively associated with gene pathways involved in hypoxia, microvasculature, stem cell plasticity, and the molecular characterisation of glioblastoma subtypes. In patient-derived glioblastoma cell lines,andwere upregulated after chemoradiation and correlated with an increase inexpression. These findings suggest that RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes.
Implications and Future Directions
- The study's findings suggest that RAS plays a role in the progression of glioblastoma and is associated with changes in the tumour microenvironment. Future research could explore the potential of targeting the RAS system as a therapeutic approach for glioblastoma. Additionally, further research could investigate the specific mechanisms by which RAS affects glioblastoma survival outcomes and the tumour microenvironment.