Upregulation of the Renin–Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma
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 (<i...
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MDPI AG
2024-04-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/7/634 |
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| author | Mathew Lozinski Eugenie R. Lumbers Nikola A. Bowden Jennifer H. Martin Michael F. Fay Kirsty G. Pringle Paul A. Tooney |
| author_facet | Mathew Lozinski Eugenie R. Lumbers Nikola A. Bowden Jennifer H. Martin Michael F. Fay Kirsty G. Pringle Paul A. Tooney |
| author_sort | Mathew Lozinski |
| collection | DOAJ |
| description | 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 (<i>ATP6AP2</i>, <i>AGTR1</i>, <i>AGTR2</i>, <i>ACE</i>, <i>AGT</i>, and <i>REN</i>) 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, <i>ATP6AP2</i>, <i>AGTR1</i>, <i>ACE</i>, and <i>AGT</i> had consistent expressions across samples, while <i>AGTR2</i> and <i>REN</i> were lowly expressed. High expression of <i>AGTR1</i> was independently associated with lower progression-free survival (PFS) (<i>p</i> = 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis (<i>p</i> = 0.095). The combined expression of RAS receptors (<i>ATP6AP2</i>, <i>AGTR1</i>, and <i>AGTR2</i>) 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, <i>ATP6AP2</i> and <i>AGTR1</i> were upregulated after chemoradiotherapy and correlated with an increase in <i>HIF1A</i> expression. This data suggests the RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes. |
| first_indexed | 2024-04-24T10:47:18Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-24T10:47:18Z |
| publishDate | 2024-04-01 |
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| spelling | doaj.art-06ad3a9f71ba462a811ae06590932a8e2024-04-12T13:16:35ZengMDPI AGCells2073-44092024-04-0113763410.3390/cells13070634Upregulation of the Renin–Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in GlioblastomaMathew Lozinski0Eugenie R. Lumbers1Nikola A. Bowden2Jennifer H. Martin3Michael F. Fay4Kirsty G. Pringle5Paul A. Tooney6School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, AustraliaSchool of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, AustraliaMark Hughes Foundation Centre for Brain Cancer Research, University of Newcastle, Callaghan, NSW 2308, AustraliaGlioblastoma 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 (<i>ATP6AP2</i>, <i>AGTR1</i>, <i>AGTR2</i>, <i>ACE</i>, <i>AGT</i>, and <i>REN</i>) 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, <i>ATP6AP2</i>, <i>AGTR1</i>, <i>ACE</i>, and <i>AGT</i> had consistent expressions across samples, while <i>AGTR2</i> and <i>REN</i> were lowly expressed. High expression of <i>AGTR1</i> was independently associated with lower progression-free survival (PFS) (<i>p</i> = 0.01) and had a non-significant trend for overall survival (OS) after multivariate analysis (<i>p</i> = 0.095). The combined expression of RAS receptors (<i>ATP6AP2</i>, <i>AGTR1</i>, and <i>AGTR2</i>) 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, <i>ATP6AP2</i> and <i>AGTR1</i> were upregulated after chemoradiotherapy and correlated with an increase in <i>HIF1A</i> expression. This data suggests the RAS is correlated with changes in the tumour microenvironment and associated with glioblastoma survival outcomes.https://www.mdpi.com/2073-4409/13/7/634glioblastomaproreninangiotensinogenhypoxiachemoradiation |
| spellingShingle | Mathew Lozinski Eugenie R. Lumbers Nikola A. Bowden Jennifer H. Martin Michael F. Fay Kirsty G. Pringle Paul A. Tooney Upregulation of the Renin–Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma Cells glioblastoma prorenin angiotensinogen hypoxia chemoradiation |
| title | Upregulation of the Renin–Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma |
| title_full | Upregulation of the Renin–Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma |
| title_fullStr | Upregulation of the Renin–Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma |
| title_full_unstemmed | Upregulation of the Renin–Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma |
| title_short | Upregulation of the Renin–Angiotensin System Is Associated with Patient Survival and the Tumour Microenvironment in Glioblastoma |
| title_sort | upregulation of the renin angiotensin system is associated with patient survival and the tumour microenvironment in glioblastoma |
| topic | glioblastoma prorenin angiotensinogen hypoxia chemoradiation |
| url | https://www.mdpi.com/2073-4409/13/7/634 |
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