Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours

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dc.contributor.authorDogan E.
dc.contributor.authorYildirim Z.
dc.contributor.authorAkalin T.
dc.contributor.authorOzgiray E.
dc.contributor.authorAkinturk N.
dc.contributor.authorAktan C.
dc.contributor.authorSolmaz A.E.
dc.date.accessioned2024-03-13T10:01:08Z
dc.date.available2024-03-13T10:01:08Z
dc.date.issued2024
dc.departmentİstanbul Beykent Üniversitesien_US
dc.description.abstractBackground: PTEN is a tumour suppressor gene and well-known for being frequently mutated in several cancer types. Loss of immunogenicity can also be attributed to PTEN loss, because of its role in establishing the tumour microenvironment. Therefore, this study aimed to represent the link between PTEN and cGAS-STING activity, a key mediator of inflammation, in tumour samples of glioblastoma patients. Methods: Tumour samples of 36 glioblastoma patients were collected. After DNA isolation, all coding regions of PTEN were sequenced and analysed. PTEN expression status was also evaluated by qRT-PCR, western blot, and immunohistochemical methods. Interferon-stimulated gene expressions, cGAMP activity, CD8 infiltration, and Granzyme B expression levels were determined especially for the evaluation of cGAS-STING activity and immunogenicity. Results: Mutant PTEN patients had significantly lower PTEN expression, both at mRNA and protein levels. Decreased STING, IRF3, NF-KB1, and RELA mRNA expressions were also found in patients with mutant PTEN. Immunohistochemistry staining of PTEN displayed expressional loss in 38.1% of the patients. Besides, patients with PTEN loss had considerably lower amounts of IFNB and IFIT2 mRNA expressions. Furthermore, CD8 infiltration, cGAMP, and Granzyme B levels were reduced in the PTEN loss group. Conclusion: This study reveals the immunosuppressive effects of PTEN loss in glioblastoma tumours via the cGAS-STING pathway. Therefore, determining the PTEN status in tumours is of great importance, like in situations when considering the treatment of glioblastoma patients with immunotherapeutic agents. © 2024, The Author(s).en_US
dc.description.sponsorshipTGA-2019-20329; Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, TÜBİTAKen_US
dc.description.sponsorshipThis work was supported by the Ege University Scientific Research Projects Coordination (TGA-2019-20329). We would like to thank Timur Kose for his statistical advice.en_US
dc.description.sponsorshipOpen access funding provided by the Scientific and Technological Research Council of Türkiye (TÜBİTAK).en_US
dc.identifier.doi10.1007/s11060-023-04556-4
dc.identifier.endpage292en_US
dc.identifier.issn0167-594X
dc.identifier.issue2en_US
dc.identifier.pmid38214828en_US
dc.identifier.scopus2-s2.0-85182172972
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage283en_US
dc.identifier.urihttps://doi.org/10.1007/s11060-023-04556-4
dc.identifier.urihttps://hdl.handle.net/20.500.12662/3012
dc.identifier.volume166en_US
dc.identifier.wosWOS:001141437900001
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofJournal of Neuro-Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectcGAS-STING pathwayen_US
dc.subjectGlioblastomaen_US
dc.subjectImmunogenicityen_US
dc.subjectInterferon responseen_US
dc.subjectPTENen_US
dc.titleInvestigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumoursen_US
dc.typeArticleen_US

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