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An emerging body of literature links the role of the renin\u2013angiotensin 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.<\/jats:p>","DOI":"10.3390\/cells13070634","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:27:52Z","timestamp":1712305672000},"page":"634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Upregulation of the Renin\u2013Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Mathew","family":"Lozinski","sequence":"first","affiliation":[{"name":"School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Mark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenie R.","family":"Lumbers","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Mothers and Babies Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-1694","authenticated-orcid":false,"given":"Nikola A.","family":"Bowden","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8614-0199","authenticated-orcid":false,"given":"Jennifer H.","family":"Martin","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Fay","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Mark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"},{"name":"GenesisCare, Gateshead, NSW 2290, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-0496","authenticated-orcid":false,"given":"Kirsty G.","family":"Pringle","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Mothers and Babies Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3745-4367","authenticated-orcid":false,"given":"Paul A.","family":"Tooney","sequence":"additional","affiliation":[{"name":"Mark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"},{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brown, N.F., Ottaviani, D., Tazare, J., Gregson, J., Kitchen, N., Brandner, S., Fersht, N., and Mulholland, P. 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