Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature
Isocitrate dehydrogenase wild-type glioblastoma (GBM) is characterised by a heterogeneous genetic landscape resulting from dynamic competition between tumour subclones to survive selective pressures. Improvements in metabolite identification and metabolome coverage have led to increased interest in...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024173409 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841526211267788800 |
|---|---|
| author | James Wood Stuart J. Smith Marcos Castellanos-Uribe Anbarasu Lourdusamy Sean T. May David A. Barrett Richard G. Grundy Dong-Hyun Kim Ruman Rahman |
| author_facet | James Wood Stuart J. Smith Marcos Castellanos-Uribe Anbarasu Lourdusamy Sean T. May David A. Barrett Richard G. Grundy Dong-Hyun Kim Ruman Rahman |
| author_sort | James Wood |
| collection | DOAJ |
| description | Isocitrate dehydrogenase wild-type glioblastoma (GBM) is characterised by a heterogeneous genetic landscape resulting from dynamic competition between tumour subclones to survive selective pressures. Improvements in metabolite identification and metabolome coverage have led to increased interest in clinically relevant applications of metabolomics. Here, we use liquid chromatography–mass spectrometry and gene expression microarray to profile integrated intratumour metabolic heterogeneity, as a direct functional readout of adaptive responses of subclones to the tumour microenvironment. Multi-region surgical sampling was performed on five adult GBM patients based on pre-operative brain imaging and fluorescence-guided surgery. Polar and hydrophobic metabolites extracted from tumour fragments were assessed, followed by putative assignment of metabolite identifications based on retention times and molecular mass. Class discrimination between tumour regions through showed clear separation of tumour regions based on polar metabolite profiles. Metabolic pathway assignments revealed several significantly altered metabolites between the tumour core and invasive region to be associated with purine and pyrimidine metabolism. This proof-of-principle study assesses intratumour heterogeneity through mass spectrometry-based metabolite profiling of multi-region biopsies. Bioinformatic interpretation of the GBM metabolome has highlighted the invasive region to be biologically distinct compared to tumour core and revealed putative drug-targetable metabolic pathways associated with purine and pyrimidine metabolism. |
| format | Article |
| id | doaj-art-920ba38d775f4871879e058b75dc07dd |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-920ba38d775f4871879e058b75dc07dd2025-01-17T04:50:52ZengElsevierHeliyon2405-84402025-01-01111e41309Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signatureJames Wood0Stuart J. Smith1Marcos Castellanos-Uribe2Anbarasu Lourdusamy3Sean T. May4David A. Barrett5Richard G. Grundy6Dong-Hyun Kim7Ruman Rahman8Children's Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, UKChildren's Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, UKNottingham Arabidopsis Stock Centre, School of Biosciences, University of Nottingham, UKChildren's Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, UKNottingham Arabidopsis Stock Centre, School of Biosciences, University of Nottingham, UKCentre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, UKChildren's Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, UKCentre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division, School of Pharmacy, University of Nottingham, UKChildren's Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, UK; Corresponding author. Children's Brain Tumour Research Centre, School of Medicine, Biodiscovery Institute, University of Nottingham, Nottingham, NG7 2RD, UK.Isocitrate dehydrogenase wild-type glioblastoma (GBM) is characterised by a heterogeneous genetic landscape resulting from dynamic competition between tumour subclones to survive selective pressures. Improvements in metabolite identification and metabolome coverage have led to increased interest in clinically relevant applications of metabolomics. Here, we use liquid chromatography–mass spectrometry and gene expression microarray to profile integrated intratumour metabolic heterogeneity, as a direct functional readout of adaptive responses of subclones to the tumour microenvironment. Multi-region surgical sampling was performed on five adult GBM patients based on pre-operative brain imaging and fluorescence-guided surgery. Polar and hydrophobic metabolites extracted from tumour fragments were assessed, followed by putative assignment of metabolite identifications based on retention times and molecular mass. Class discrimination between tumour regions through showed clear separation of tumour regions based on polar metabolite profiles. Metabolic pathway assignments revealed several significantly altered metabolites between the tumour core and invasive region to be associated with purine and pyrimidine metabolism. This proof-of-principle study assesses intratumour heterogeneity through mass spectrometry-based metabolite profiling of multi-region biopsies. Bioinformatic interpretation of the GBM metabolome has highlighted the invasive region to be biologically distinct compared to tumour core and revealed putative drug-targetable metabolic pathways associated with purine and pyrimidine metabolism.http://www.sciencedirect.com/science/article/pii/S2405844024173409GlioblastomaMetabolomicsInvasive marginLiquid-chromatography mass spectrometry |
| spellingShingle | James Wood Stuart J. Smith Marcos Castellanos-Uribe Anbarasu Lourdusamy Sean T. May David A. Barrett Richard G. Grundy Dong-Hyun Kim Ruman Rahman Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature Heliyon Glioblastoma Metabolomics Invasive margin Liquid-chromatography mass spectrometry |
| title | Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature |
| title_full | Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature |
| title_fullStr | Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature |
| title_full_unstemmed | Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature |
| title_short | Metabolomic characterisation of the glioblastoma invasive margin reveals a region-specific signature |
| title_sort | metabolomic characterisation of the glioblastoma invasive margin reveals a region specific signature |
| topic | Glioblastoma Metabolomics Invasive margin Liquid-chromatography mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024173409 |
| work_keys_str_mv | AT jameswood metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature AT stuartjsmith metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature AT marcoscastellanosuribe metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature AT anbarasulourdusamy metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature AT seantmay metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature AT davidabarrett metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature AT richardggrundy metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature AT donghyunkim metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature AT rumanrahman metabolomiccharacterisationoftheglioblastomainvasivemarginrevealsaregionspecificsignature |