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Upregulation of the Renin-Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma.
Lozinski, Mathew; Lumbers, Eugenie R; Bowden, Nikola A; Martin, Jennifer H; Fay, Michael F; Pringle, Kirsty G; Tooney, Paul A.
Afiliación
  • Lozinski M; School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Lumbers ER; Mark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Bowden NA; Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
  • Martin JH; School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Fay MF; Mothers and Babies Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
  • Pringle KG; School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia.
  • Tooney PA; Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia.
Cells ; 13(7)2024 Apr 05.
Article en En | MEDLINE | ID: mdl-38607073
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 (ATP6AP2, AGTR1, AGTR2, ACE, AGT, and REN) 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, ATP6AP2, AGTR1, ACE, and AGT had consistent expressions across samples, while AGTR2 and REN were lowly expressed. High expression of AGTR1 was independently associated with lower progression-free survival (PFS) (p = 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis (p = 0.095). The combined expression of RAS receptors (ATP6AP2, AGTR1, and AGTR2) 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, ATP6AP2 and AGTR1 were upregulated after chemoradiotherapy and correlated with an increase in HIF1A expression. This data suggests the RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Renina-Angiotensina / Glioblastoma Límite: Humans Idioma: En Revista: Cells Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Renina-Angiotensina / Glioblastoma Límite: Humans Idioma: En Revista: Cells Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Suiza