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73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

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PGRMC1 is a prognostic factor in glioblastoma and modulates glioblastoma progression and response to therapy

PGRMC1 ist ein prognostischer Faktor im Glioblastom und beeinflusst die Tumorprogression und das Therapieansprechen

Meeting Abstract

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  • presenting/speaker Hannah Schröder - Universitätsklinikum Magdeburg, Klinik für Neurochirurgie, Magdeburg, Deutschland
  • Nina Kreße - Universitätsklinikum Magdeburg, Klinik für Neurochirurgie, Magdeburg, Deutschland
  • Frederik Schäfer - Universitätsklinikum Magdeburg, Klinik für Neurochirurgie, Magdeburg, Deutschland
  • Klaus-Peter Stein - Universitätsklinikum Magdeburg, Klinik für Neurochirurgie, Magdeburg, Deutschland
  • Christian Mawrin - Universitätsklinikum Magdeburg, Institut für Neuropathologie, Magdeburg, Deutschland
  • Claudia A. Dumitru - Universitätsklinikum Magdeburg, Klinik für Neurochirurgie, Magdeburg, Deutschland
  • I. Erol Sandalcioglu - Universitätsklinikum Magdeburg, Klinik für Neurochirurgie, Magdeburg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV265

doi: 10.3205/22dgnc257, urn:nbn:de:0183-22dgnc2575

Published: May 25, 2022

© 2022 Schröder et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

Text

Objective: Progesterone receptor membrane component 1 (PGRMC1) is emerging as an important tumor-promoting factor in solid cancers. The role of PGRMC1 in glioblastoma (GBM) pathophysiology is, however, currently unkwown.

Methods: PGRMC1 expression was determined by immunhistochemistry in two independent cohorts of GBM patients (n1=155 and n2=212). Association with the patients’ outcome was tested by Kaplan-Meier, log-rank and multivariate Cox regression analysis. The effect of PGRMC1 regarding proliferation, anchorage-independent growth, invasion and response to therapy was analysed in two different GBM cell lines stably transfected to downregulate PGRMC1. Potential downstream molecular mechanisms of PGRMC1 were assessed both in vitro and in situ.

Results: High levels of PGRMC1 significantly associated with (p1=0.003, p2=0.021; log-rank) and predicted (cohort 1: HR=1.505, CI[95%]=1.043-2.171, p=0.029; cohort 2: HR=1.505, CI[95%]=1.085-2.088, p=0.014; Cox regression) poor overall survival in both cohorts of GBM patients. In vitro, PGRMC1 promoted the proliferation, anchorage-independent growth and invasion of GBM cells. Both Integrin beta-1 (ITGB1) and TCF 1/7 were downstream of PGRMC1 in vitro. The levels of ITGB1 and PGRMC1 also correlated significantly (p<0.001, Rho=0.244; Spearman) in tissues from GBM patients. Finally, PGRMC1 rendered GBM cells less susceptible to the standard GBM chemotherapeutic agent temozolomide but significantly more susceptible to the ferroptosis inducer erastin

Conclusion: PGRMC1 is an unfavorable prognostic factor for GBM patients and promotes GBM progression as well as resistance to the current standard of care therapy. However, PGRMC1 might be a promising target for novel therapeutic strategies using ferroptosis inducers in this type of cancer.