期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/ijms23062949
关键词
glioblastoma; MALDI-IMS lipidomics; temozolomide; modular gene expression; molecular subtypes; lipid metabolism
资金
- Research Unit of the University Hospital Son Espases
- Basque Government [IT1162-19]
- Institute of Health Carlos III [PI16/02200]
- EC (European Regional Development Fund, ERDF) [CP12/03338]
- Govern Balear (Direccio General d'Innovacio i Recerca) [FPI/2160/2018, FPI/1787/2015]
- ESF (European Social Fund)
- Govern Balear (Servei d'Ocupacio de les IIles Balears and Garantia Juvenil) [JQ-SP 18/17]
- ESF
- Institute of Health Carlos III
- ERDF (Miguel Servet II program) [CPII17/00005]
This study explores the effects of temozolomide (TMZ) treatment on the lipid composition of healthy brain tissue and glioblastoma (GBM), and investigates the potential therapeutic approaches for GBM and ways to reduce TMZ side effects. The researchers found that certain bioactive lipid metabolic hubs were altered in healthy brain tissue treated with TMZ, and verified the link between GBM subtypes and patient survival with the expression of enzymes responsible for the observed lipid changes.
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.
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