Liyen K Kan, Matthew Drill, Andrea Muscat, Paul Sanfilippo, Richard P Sequeira, Padmakrishnan C Jayakrishnan, Anh Vo, Nicholas C Wong, Marian Todaro, Catriona McLean, Katherine J Drummond, Martin Hunn, David A Williams, Terence J O'Brien, Mastura Monif
{"title":"Characterisation of the expression of P2X7 receptor, cancer stem cell markers and immunological mediators in human high-grade gliomas.","authors":"Liyen K Kan, Matthew Drill, Andrea Muscat, Paul Sanfilippo, Richard P Sequeira, Padmakrishnan C Jayakrishnan, Anh Vo, Nicholas C Wong, Marian Todaro, Catriona McLean, Katherine J Drummond, Martin Hunn, David A Williams, Terence J O'Brien, Mastura Monif","doi":"10.1186/s12868-025-00973-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma is the most aggressive primary brain cancer. It is considered an 'immunologically cold' tumour where immune infiltrates are polarised to drive immunosuppression-and therefore tumour proliferation. An important driver of neuroinflammation in glioma is the purinergic P2X7 receptor (P2X7R). While much of the complex glioma microenvironment has been characterised, studies expounding the associations between various cytokines/chemokines, immune cell markers, P2X7R expression and glioma stemness are lacking. Here we aimed to characterise the mRNA expression profiles of various tumour markers, and common 'pro-' and 'anti-tumour' inflammatory mediators, and correlate this to P2X7R expression in human high-grade glioma samples compared to 'healthy' non-tumour post-mortem brain.</p><p><strong>Methods: </strong>High grade gliomas were collected from 34 patients undergoing routine tumour resection surgery and compared to 12 'healthy' post-mortem controls. High throughput qPCR was performed on extracted RNA converted to cDNA to examine a custom-made panel of 38 tumour and immune related genes.</p><p><strong>Results: </strong>Markers of innate immunity including CD68, S100A9, HLADR, NLPR3, interleukin (IL) 1β, IL-6, TNFα and NF-κB were significantly increased in human derived glioblastoma samples compared to healthy control brain. P2X7R was also upregulated in the glioma microenvironment and its expression was linked to the expression of VEGFB, MMP9, PCNA, IL-4 and IL-8. The level of expression of P2X7R was not associated with overall survival in high grade gliomas.</p><p><strong>Discussion: </strong>Collectively, this study confirms the significant overexpression of P2X7R in human high-grade gliomas as well as highlights the presence of a multidirectional neuroinflammatory milieu in which both tumour-promoting and tumour-suppressive genes are overexpressed.</p>","PeriodicalId":9031,"journal":{"name":"BMC Neuroscience","volume":"26 1","pages":"59"},"PeriodicalIF":2.3000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12868-025-00973-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Glioblastoma is the most aggressive primary brain cancer. It is considered an 'immunologically cold' tumour where immune infiltrates are polarised to drive immunosuppression-and therefore tumour proliferation. An important driver of neuroinflammation in glioma is the purinergic P2X7 receptor (P2X7R). While much of the complex glioma microenvironment has been characterised, studies expounding the associations between various cytokines/chemokines, immune cell markers, P2X7R expression and glioma stemness are lacking. Here we aimed to characterise the mRNA expression profiles of various tumour markers, and common 'pro-' and 'anti-tumour' inflammatory mediators, and correlate this to P2X7R expression in human high-grade glioma samples compared to 'healthy' non-tumour post-mortem brain.
Methods: High grade gliomas were collected from 34 patients undergoing routine tumour resection surgery and compared to 12 'healthy' post-mortem controls. High throughput qPCR was performed on extracted RNA converted to cDNA to examine a custom-made panel of 38 tumour and immune related genes.
Results: Markers of innate immunity including CD68, S100A9, HLADR, NLPR3, interleukin (IL) 1β, IL-6, TNFα and NF-κB were significantly increased in human derived glioblastoma samples compared to healthy control brain. P2X7R was also upregulated in the glioma microenvironment and its expression was linked to the expression of VEGFB, MMP9, PCNA, IL-4 and IL-8. The level of expression of P2X7R was not associated with overall survival in high grade gliomas.
Discussion: Collectively, this study confirms the significant overexpression of P2X7R in human high-grade gliomas as well as highlights the presence of a multidirectional neuroinflammatory milieu in which both tumour-promoting and tumour-suppressive genes are overexpressed.
期刊介绍：
BMC Neuroscience is an open access, peer-reviewed journal that considers articles on all aspects of neuroscience, welcoming studies that provide insight into the molecular, cellular, developmental, genetic and genomic, systems, network, cognitive and behavioral aspects of nervous system function in both health and disease. Both experimental and theoretical studies are within scope, as are studies that describe methodological approaches to monitoring or manipulating nervous system function.
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