Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype
Glioblastoma (GBM) represents one of the deadliest tumors owing to a lack of effective treatments. The adverse outcomes are worsened by high rates of treatment discontinuation, caused by the severe side effects of temozolomide (TMZ), the reference treatment. Therefore, understanding TMZ’s effects on...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/2949 |
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| author | Albert Maimó-Barceló Lucía Martín-Saiz José A. Fernández Karim Pérez-Romero Santiago Garfias-Arjona Mónica Lara-Almúnia Javier Piérola-Lopetegui Joan Bestard-Escalas Gwendolyn Barceló-Coblijn |
| author_facet | Albert Maimó-Barceló Lucía Martín-Saiz José A. Fernández Karim Pérez-Romero Santiago Garfias-Arjona Mónica Lara-Almúnia Javier Piérola-Lopetegui Joan Bestard-Escalas Gwendolyn Barceló-Coblijn |
| author_sort | Albert Maimó-Barceló |
| collection | DOAJ |
| description | Glioblastoma (GBM) represents one of the deadliest tumors owing to a lack of effective treatments. The adverse outcomes are worsened by high rates of treatment discontinuation, caused by the severe side effects of temozolomide (TMZ), the reference treatment. Therefore, understanding TMZ’s effects on GBM and healthy brain tissue could reveal new approaches to address chemotherapy side effects. In this context, we have previously demonstrated the membrane lipidome is highly cell type-specific and very sensitive to pathophysiological states. However, little remains known as to how membrane lipids participate in GBM onset and progression. Hence, we employed an ex vivo model to assess the impact of TMZ treatment on healthy and GBM lipidome, which was established through imaging mass spectrometry techniques. This approach revealed that bioactive lipid metabolic hubs (phosphatidylinositol and phosphatidylethanolamine plasmalogen species) were altered in healthy brain tissue treated with TMZ. To better understand these changes, we interrogated RNA expression and DNA methylation datasets of the Cancer Genome Atlas database. The results enabled GBM subtypes and patient survival to be linked with the expression of enzymes accounting for the observed lipidome, thus proving that exploring the lipid changes could reveal promising therapeutic approaches for GBM, and ways to ameliorate TMZ side effects. |
| first_indexed | 2024-03-09T19:43:31Z |
| format | Article |
| id | doaj.art-91d70fd44b664a229f0b65b4d0a787fc |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:43:31Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-91d70fd44b664a229f0b65b4d0a787fc2023-11-24T01:29:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236294910.3390/ijms23062949Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular SubtypeAlbert Maimó-Barceló0Lucía Martín-Saiz1José A. Fernández2Karim Pérez-Romero3Santiago Garfias-Arjona4Mónica Lara-Almúnia5Javier Piérola-Lopetegui6Joan Bestard-Escalas7Gwendolyn Barceló-Coblijn8Institut d’Investigacio Sanitaria Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, SpainDepartment of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, SpainDepartment of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, SpainInstitut d’Investigacio Sanitaria Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, SpainQuirónsalud Medical Center, 07300 Inca, SpainDepartment of Neurosurgery, Jimenez Diaz Foundation University Hospital, Reyes Catolicos Av., No 2, 28040 Madrid, SpainInstitut d’Investigacio Sanitaria Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, SpainBioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, 1200 Bruxelles, BelgiumInstitut d’Investigacio Sanitaria Illes Balears (IdISBa, Health Research Institute of the Balearic Islands), 07120 Palma, SpainGlioblastoma (GBM) represents one of the deadliest tumors owing to a lack of effective treatments. The adverse outcomes are worsened by high rates of treatment discontinuation, caused by the severe side effects of temozolomide (TMZ), the reference treatment. Therefore, understanding TMZ’s effects on GBM and healthy brain tissue could reveal new approaches to address chemotherapy side effects. In this context, we have previously demonstrated the membrane lipidome is highly cell type-specific and very sensitive to pathophysiological states. However, little remains known as to how membrane lipids participate in GBM onset and progression. Hence, we employed an ex vivo model to assess the impact of TMZ treatment on healthy and GBM lipidome, which was established through imaging mass spectrometry techniques. This approach revealed that bioactive lipid metabolic hubs (phosphatidylinositol and phosphatidylethanolamine plasmalogen species) were altered in healthy brain tissue treated with TMZ. To better understand these changes, we interrogated RNA expression and DNA methylation datasets of the Cancer Genome Atlas database. The results enabled GBM subtypes and patient survival to be linked with the expression of enzymes accounting for the observed lipidome, thus proving that exploring the lipid changes could reveal promising therapeutic approaches for GBM, and ways to ameliorate TMZ side effects.https://www.mdpi.com/1422-0067/23/6/2949glioblastomaMALDI-IMS lipidomicstemozolomidemodular gene expressionmolecular subtypeslipid metabolism |
| spellingShingle | Albert Maimó-Barceló Lucía Martín-Saiz José A. Fernández Karim Pérez-Romero Santiago Garfias-Arjona Mónica Lara-Almúnia Javier Piérola-Lopetegui Joan Bestard-Escalas Gwendolyn Barceló-Coblijn Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype International Journal of Molecular Sciences glioblastoma MALDI-IMS lipidomics temozolomide modular gene expression molecular subtypes lipid metabolism |
| title | Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype |
| title_full | Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype |
| title_fullStr | Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype |
| title_full_unstemmed | Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype |
| title_short | Polyunsaturated Fatty Acid-Enriched Lipid Fingerprint of Glioblastoma Proliferative Regions Is Differentially Regulated According to Glioblastoma Molecular Subtype |
| title_sort | polyunsaturated fatty acid enriched lipid fingerprint of glioblastoma proliferative regions is differentially regulated according to glioblastoma molecular subtype |
| topic | glioblastoma MALDI-IMS lipidomics temozolomide modular gene expression molecular subtypes lipid metabolism |
| url | https://www.mdpi.com/1422-0067/23/6/2949 |
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