The genomic alterations in glioblastoma influence the levels of CSF metabolites

Autor: Daniel H. Wang, Yoko Fujita, Antonio Dono, Ana G. Rodriguez Armendariz, Mauli Shah, Nagireddy Putluri, Pavel S. Pichardo-Rojas, Chirag B. Patel, Jay-Jiguang Zhu, Jason T. Huse, Brittany C. Parker Kerrigan, Frederick F. Lang, Yoshua Esquenazi, Leomar Y. Ballester
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Acta Neuropathologica Communications, Vol 12, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2051-5960
DOI: 10.1186/s40478-024-01722-1
Popis: Abstract Cerebrospinal fluid (CSF) analysis is underutilized in patients with glioblastoma (GBM), partly due to a lack of studies demonstrating the clinical utility of CSF biomarkers. While some studies show the utility of CSF cell-free DNA analysis, studies analyzing CSF metabolites in patients with glioblastoma are limited. Diffuse gliomas have altered cellular metabolism. For example, mutations in isocitrate dehydrogenase enzymes (e.g., IDH1 and IDH2) are common in diffuse gliomas and lead to increased levels of D-2-hydroxyglutarate in CSF. However, there is a poor understanding of changes CSF metabolites in GBM patients. In this study, we performed targeted metabolomic analysis of CSF from n = 31 patients with GBM and n = 13 individuals with non-neoplastic conditions (controls), by mass spectrometry. Hierarchical clustering and sparse partial least square-discriminant analysis (sPLS-DA) revealed differences in CSF metabolites between GBM and control CSF, including metabolites associated with fatty acid oxidation and the gut microbiome (i.e., carnitine, 2-methylbutyrylcarnitine, shikimate, aminobutanal, uridine, N-acetylputrescine, and farnesyl diphosphate). In addition, we identified differences in CSF metabolites in GBM patients based on the presence/absence of TP53 or PTEN mutations, consistent with the idea that different mutations have different effects on tumor metabolism. In summary, our results increase the understanding of CSF metabolites in patients with diffuse gliomas and highlight several metabolites that could be informative biomarkers in patients with GBM.
Databáze: Directory of Open Access Journals
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