Regional profiling reveals a distinct glioblastoma infiltrative margin proteome
Abstract Isocitrate dehydrogenase wild-type glioblastoma, a malignant brain tumour of glial origin, confers a poor prognosis with a median survival of 12 to 16 months from diagnosis. Glioblastomas are aggressive tumours that rapidly proliferate and diffusely infiltrate surrounding brain tissue. Curr...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-09228-z |
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| author | Artur Kocon Stuart J. Smith Benito Morentin Luis F. Callado Wayne Carter Ruman Rahman |
| author_facet | Artur Kocon Stuart J. Smith Benito Morentin Luis F. Callado Wayne Carter Ruman Rahman |
| author_sort | Artur Kocon |
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| description | Abstract Isocitrate dehydrogenase wild-type glioblastoma, a malignant brain tumour of glial origin, confers a poor prognosis with a median survival of 12 to 16 months from diagnosis. Glioblastomas are aggressive tumours that rapidly proliferate and diffusely infiltrate surrounding brain tissue. Current multimodal standard treatment is typically ineffective and despite gross total surgical resection, tumours recur with more aggressive sub-clonal populations of malignant cells. A defining characteristic of glioblastoma is its highly heterogeneous nature and acquirement of somatic mutations advantageous to tumour growth and suppression of apoptotic pathways. Pathogenesis of malignant brain tumours as well as its mode of transformation to a more aggressive subtype is still largely unknown. Although genomic studies have elucidated a plethora of genetic markers associated with glioblastoma subtypes, only a few have been utilised in a clinical setting. One of the emerging approaches to studying glioblastomas is by investigating how an active proteome contributes to its aggressive nature. Furthermore, through activation of specific pathways via post-translational modifications of proteins such as phosphorylation, glioblastomas create an intricate network of signalling pathways which favour tumour growth and proliferation. Here, we investigated the feasibility of diverse methodological approaches to describe abnormal protein signalling across distinct intra-tumour regions of primary glioblastoma tissue, including proliferative core, peripheral rim, and invasive margin. Whilst we observe a broadly comparable proteome relative to the human non-diseased brain, we identify cytoplasmic proteins α-trypsin, actin, apolipoprotein A1 and transthyretin which may putatively be associated with the GBM infiltrative tumour margin. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-e2e06c0bc4234623830368092b5fc5872025-08-20T04:01:34ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-09228-zRegional profiling reveals a distinct glioblastoma infiltrative margin proteomeArtur Kocon0Stuart J. Smith1Benito Morentin2Luis F. Callado3Wayne Carter4Ruman Rahman5Clinical Toxicology Research Group, School of Medicine, Royal Derby Hospital Centre, University of NottinghamSchool of Medicine, Biodiscovery Institute, University of Nottingham, University ParkSection of Forensic Pathology, Basque Institute of Legal MedicineBioBizkaia Health Research InstituteClinical Toxicology Research Group, School of Medicine, Royal Derby Hospital Centre, University of NottinghamSchool of Medicine, Biodiscovery Institute, University of Nottingham, University ParkAbstract Isocitrate dehydrogenase wild-type glioblastoma, a malignant brain tumour of glial origin, confers a poor prognosis with a median survival of 12 to 16 months from diagnosis. Glioblastomas are aggressive tumours that rapidly proliferate and diffusely infiltrate surrounding brain tissue. Current multimodal standard treatment is typically ineffective and despite gross total surgical resection, tumours recur with more aggressive sub-clonal populations of malignant cells. A defining characteristic of glioblastoma is its highly heterogeneous nature and acquirement of somatic mutations advantageous to tumour growth and suppression of apoptotic pathways. Pathogenesis of malignant brain tumours as well as its mode of transformation to a more aggressive subtype is still largely unknown. Although genomic studies have elucidated a plethora of genetic markers associated with glioblastoma subtypes, only a few have been utilised in a clinical setting. One of the emerging approaches to studying glioblastomas is by investigating how an active proteome contributes to its aggressive nature. Furthermore, through activation of specific pathways via post-translational modifications of proteins such as phosphorylation, glioblastomas create an intricate network of signalling pathways which favour tumour growth and proliferation. Here, we investigated the feasibility of diverse methodological approaches to describe abnormal protein signalling across distinct intra-tumour regions of primary glioblastoma tissue, including proliferative core, peripheral rim, and invasive margin. Whilst we observe a broadly comparable proteome relative to the human non-diseased brain, we identify cytoplasmic proteins α-trypsin, actin, apolipoprotein A1 and transthyretin which may putatively be associated with the GBM infiltrative tumour margin.https://doi.org/10.1038/s41598-025-09228-zGlioblastoma2D-PAGEProteomicsTandem mass spectrometry |
| spellingShingle | Artur Kocon Stuart J. Smith Benito Morentin Luis F. Callado Wayne Carter Ruman Rahman Regional profiling reveals a distinct glioblastoma infiltrative margin proteome Scientific Reports Glioblastoma 2D-PAGE Proteomics Tandem mass spectrometry |
| title | Regional profiling reveals a distinct glioblastoma infiltrative margin proteome |
| title_full | Regional profiling reveals a distinct glioblastoma infiltrative margin proteome |
| title_fullStr | Regional profiling reveals a distinct glioblastoma infiltrative margin proteome |
| title_full_unstemmed | Regional profiling reveals a distinct glioblastoma infiltrative margin proteome |
| title_short | Regional profiling reveals a distinct glioblastoma infiltrative margin proteome |
| title_sort | regional profiling reveals a distinct glioblastoma infiltrative margin proteome |
| topic | Glioblastoma 2D-PAGE Proteomics Tandem mass spectrometry |
| url | https://doi.org/10.1038/s41598-025-09228-z |
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