Abstract
Simple SummaryThis study aims to explore metabolic remodeling in plasma and tissue samples in patients with glioblastoma through an integrated targeted and untargeted metabolomics-based strategy. We report phospholipids, sphingomyelins, acylcarnitines, and acylglycerols as key impaired metabolic classes in glioblastoma.(1) Background: Glioblastoma is the most common malignant brain tumor in adults. Its etiology remains unknown in most cases. Glioblastoma pathogenesis consists of a progressive infiltration of the white matter by tumoral cells leading to progressive neurological deficit, epilepsy, and/or intracranial hypertension. The mean survival is between 15 to 17 months. Given this aggressive prognosis, there is an urgent need for a better understanding of the underlying mechanisms of glioblastoma to unveil new diagnostic strategies and therapeutic targets through a deeper understanding of its biology. (2) Methods: To systematically address this issue, we performed targeted and untargeted metabolomics-based investigations on both tissue and plasma samples from patients with glioblastoma. (3) Results: This study revealed 176 differentially expressed lipids and metabolites, 148 in plasma and 28 in tissue samples. Main biochemical classes include phospholipids, acylcarnitines, sphingomyelins, and triacylglycerols. Functional analyses revealed deep metabolic remodeling in glioblastoma lipids and energy substrates, which unveils the major role of lipids in tumor progression by modulating its own environment. (4) Conclusions: Overall, our study demonstrates in situ and systemic metabolic rewiring in glioblastoma that could shed light on its underlying biological plasticity and progression to inform diagnosis and/or therapeutic strategies.
Highlights
Glioblastoma (GBM) is the most common malignant brain tumor in adults [1]
The mean glioblastoma showed a male predominance of 82%
The discovery of the Isocitrate Dehydrogenase (IDH) metabolic pathway has revived this antimetabolic approach, which aims at reducing the synthesis of these molecules, which play an essential role in tumor development and progression [61]
Summary
Glioblastoma (GBM) is the most common malignant brain tumor in adults [1]. Its incidence, 2 to 5 per 100,000 [1,2], is still increasing [3,4], and its etiology remains unknown in most cases. Despite many therapeutic trials [11,12,13], the prognosis of glioblastoma is poor, with a mean survival between 15 to 17 months [14]. During the last few years, Precision Medicine (PM) has been a new paradigm that has opened a new era in personalized diagnosis and therapeutic approaches in oncology [15,16,17,18]. It is a tailored approach in disease management driven by the patient’s attributes to deliver personalized healthcare. Omics are technologies that allow for a multilayer molecular deciphering of the cell, tissue, and organism in a holistic fashion
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