Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical Course

Objective: Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. Methods: A total...

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Main Authors: Alexander Quiring, Hannah Spielmann, Fritz Teping, Safwan Saffour, Fatemeh Khafaji, Walter Schulz-Schaeffer, Nathan Monfroy, Joachim Oertel, Stefan Linsler, Christoph Sippl
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/9/2078
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author Alexander Quiring
Hannah Spielmann
Fritz Teping
Safwan Saffour
Fatemeh Khafaji
Walter Schulz-Schaeffer
Nathan Monfroy
Joachim Oertel
Stefan Linsler
Christoph Sippl
author_facet Alexander Quiring
Hannah Spielmann
Fritz Teping
Safwan Saffour
Fatemeh Khafaji
Walter Schulz-Schaeffer
Nathan Monfroy
Joachim Oertel
Stefan Linsler
Christoph Sippl
author_sort Alexander Quiring
collection DOAJ
description Objective: Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. Methods: A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of <i>MGMT</i>, <i>p15</i>, and <i>p16</i> methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results. Results: Instability was observed in all examined epigenetic markers. <i>MGMT</i> methylation changed in 30% of patients, <i>p15</i> methylation changed in 35%, and <i>p16</i> methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results. Conclusions: Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers.
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spelling doaj-art-d32689688e414bbabbed2aba2148e8632025-08-20T01:56:10ZengMDPI AGBiomedicines2227-90592024-09-01129207810.3390/biomedicines12092078Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical CourseAlexander Quiring0Hannah Spielmann1Fritz Teping2Safwan Saffour3Fatemeh Khafaji4Walter Schulz-Schaeffer5Nathan Monfroy6Joachim Oertel7Stefan Linsler8Christoph Sippl9Department of Neurosurgery, Klinikum Rechts Der Isar, Technical University Munich School of Medicine, 80333 Munich, GermanyDepartment of Neurosurgery, Faculty of Medicine, Saarland University, 66421 Homburg/Saar, GermanyDepartment of Neurosurgery, Faculty of Medicine, Saarland University, 66421 Homburg/Saar, GermanyDepartment of Neurosurgery, Medical Campus Oberfranken of FAU Erlangen, 91054 Bayreuth, GermanyDepartment of Neurosurgery, Medical Campus Oberfranken of FAU Erlangen, 91054 Bayreuth, GermanyInstitute of Neuropathology, Faculty of Medicine, Saarland University, 66421 Homburg/Saar, GermanyDepartment of Neurosurgery, Faculty of Medicine, Saarland University, 66421 Homburg/Saar, GermanyDepartment of Neurosurgery, Faculty of Medicine, Saarland University, 66421 Homburg/Saar, GermanyDepartment of Neurosurgery, Medical Campus Oberfranken of FAU Erlangen, 91054 Bayreuth, GermanyDepartment of Neurosurgery, Medical Campus Oberfranken of FAU Erlangen, 91054 Bayreuth, GermanyObjective: Epigenetic tumor characteristics are in focus for glioblastoma prognosis. This raises the question if these characteristics present with stable expression during the progression of the disease, and if potential temporal instability might influence their prognostic value. Methods: A total of 44 patients suffering from glioblastoma who were treated for their primary and relapse tumors were included in the study. Tumor specimens from the initial and recurrent tumor resection were subjected to evaluation of <i>MGMT</i>, <i>p15</i>, and <i>p16</i> methylation statuses. MiRNA-21, -24, -26a, and -181d expression was evaluated as well. The stability of these epigenetic markers during the progression of the disease was correlated with further clinical data. A Cancer Genome Atlas (TCGA) dataset of 224 glioblastoma patients was used as an independent cohort to validate the results. Results: Instability was observed in all examined epigenetic markers. <i>MGMT</i> methylation changed in 30% of patients, <i>p15</i> methylation changed in 35%, and <i>p16</i> methylation changed in 37.5% of cases. MiRNA expression in corresponding initial and relapse tumor specimens varied considerably in general, individual cases presented with a stable expression. Patients with a decreased expression of miRNA-21 in their recurrence tumor showed significantly longer overall survival. These results are supported by the data from TCGA indicating similar results. Conclusions: Epigenetic characteristics may change during the course of glioblastoma disease. This may influence the prognostic value of derived molecular markers.https://www.mdpi.com/2227-9059/12/9/2078glioblastoma micro-RNAepigeneticmethylationrecurrence
spellingShingle Alexander Quiring
Hannah Spielmann
Fritz Teping
Safwan Saffour
Fatemeh Khafaji
Walter Schulz-Schaeffer
Nathan Monfroy
Joachim Oertel
Stefan Linsler
Christoph Sippl
Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical Course
Biomedicines
glioblastoma micro-RNA
epigenetic
methylation
recurrence
title Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical Course
title_full Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical Course
title_fullStr Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical Course
title_full_unstemmed Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical Course
title_short Epigenetic Characteristics in Primary and Recurrent Glioblastoma—Influence on the Clinical Course
title_sort epigenetic characteristics in primary and recurrent glioblastoma influence on the clinical course
topic glioblastoma micro-RNA
epigenetic
methylation
recurrence
url https://www.mdpi.com/2227-9059/12/9/2078
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