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Investigating the effects of PTEN mutations on cGAS-STING pathway in glioblastoma tumours.
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.
Afiliación
  • Dogan E; Department of Medical Biology, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Yildirim Z; Department of Medical Biology, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Akalin T; Department of Pathology, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Ozgiray E; Department of Neurosurgery, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Akinturk N; Department of Neurosurgery, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Aktan C; Department of Medical Biology, Beykent University School of Medicine, Istanbul, Türkiye.
  • Solmaz AE; Department of Medical Genetics, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Biceroglu H; Department of Neurosurgery, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Caliskan KE; Department of Neurosurgery, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Ertan Y; Department of Pathology, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Yurtseven T; Department of Neurosurgery, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Kosova B; Department of Medical Biology, Ege University Faculty of Medicine, Izmir, Türkiye.
  • Bozok V; Department of Medical Biology, Ege University Faculty of Medicine, Izmir, Türkiye. vldnbozok@gmail.com.
J Neurooncol ; 166(2): 283-292, 2024 Jan.
Article en En | MEDLINE | ID: mdl-38214828
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glioblastoma Límite: Humans Idioma: En Revista: J Neurooncol Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Glioblastoma Límite: Humans Idioma: En Revista: J Neurooncol Año: 2024 Tipo del documento: Article