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Date
2025-09-15
Authors
Publisher
Philipps-Universität Marburg
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Abstract
Glioblastomas are the most common brain tumours and, with a median survival time of around 15 months after initial diagnosis, are among the most aggressive tumour types in humans. A fundamental problem is the reliable diagnosis of GBM recurrences, which are often characterised by a pronounced resistance to established radiotherapy and chemo-therapy. The search for new diagnostic and therapeutic approaches is therefore an im-portant aspect of neuro-oncological research.
The aim of this study was to investigate the three tumour proteins ASAH1, SYNM and GPNMB, which proved to be promising in a mass spectrometric search test, with regard to their potential as diagnostic biomarkers for GBM recurrences and therapeutic target molecules. While ASAH1 is known as an enzyme of ceramide metabolism and converts proapoptotic ceramides into growth-promoting sphingosine, GPNMB as a transmem-brane protein plays a role in tumour progression towards more aggressive subtypes and is detectable in the tumour microenvironment. SYNM, on the other hand, is an intermedi-ate filament and influences tumour cell proliferation and migration.
A cohort of 20 patients who had undergone surgical resection of both an initial GBM and a recurrence was retrospectively analysed. Protein concentrations and mRNA expres-sion were measured in the corresponding tumour tissue samples using RT-qPCR, West-ern blot, ELISA and immunohisto- and immunofluorescence staining. The tissue from the tumour recurrences showed a higher protein concentration than the initial findings. In order to investigate the suitability of the molecules as biomarkers for GBM recurrences in liquid biopsies, serum samples taken from 14 patients before the operations were also analysed for congruence with the results from the tissue samples. However, the differ-ences in concentration between initial and relapsed GBM were not significant here, meaning that individual molecules do not provide sufficient diagnostic certainty as bi-omarkers.
The present study contributes to a better tumour-biological understanding of glioblasto-ma recurrences. The investigated proteins could be used as part of molecular clusters and as therapeutic targets, in particular to increase the radiation and chemosensitivity of GBM recurrences. In addition, the investigation of CSF samples as an alternative materi-al for liquid biopsies offers promising perspectives for future research. Further studies are required to validate the diagnostic and therapeutic relevance of these approaches.
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Dates
Created: 2025Issued: 2025-09-15Updated: 2025-09-15
Faculty
Medizin
Language
ger
Data types
DoctoralThesis
DFG-subjects
Liquid BiopsyBiomarkerGlioblastomMolekulare OnkologieNeuroonkologieGBM
DDC-Numbers
610
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Haberl, Zeno: Analyse von potenziellen Protein-Biomarkern in einer Glioblastom-Patientenkohorte. : Philipps-Universität Marburg 2025-09-15. DOI: https://doi.org/10.17192/z2025.0445.
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