دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours
المؤلفون: Dogan, Eda, Yildirim, Zafer, Akalin, Taner, Ozgiray, Erkin, Akinturk, Nevhis, Aktan, Cagdas, Solmaz, Asli Ece, Biceroglu, Huseyin, Caliskan, Kadri Emre, Ertan, Yesim, Yurtseven, Taskin, Kosova, Buket, Bozok, Vildan
المساهمون: Ege University
المصدر: Journal of Neuro-Oncology ; volume 166, issue 2, page 283-292 ; ISSN 0167-594X 1573-7373
بيانات النشر: Springer Science and Business Media LLC
سنة النشر: 2024
مصطلحات موضوعية: Cancer Research, Neurology (clinical), Neurology, Oncology
الوصف: Background 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1007/s11060-023-04556-4
DOI: 10.1007/s11060-023-04556-4.pdf
DOI: 10.1007/s11060-023-04556-4/fulltext.html
الإتاحة: https://doi.org/10.1007/s11060-023-04556-4Test
حقوق: https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test
رقم الانضمام: edsbas.EDE39A5B
قاعدة البيانات: BASE