The genomic alterations in glioblastoma influence the levels of CSF metabolites.
The genomic alterations in glioblastoma influence the levels of CSF metabolites.
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胶质母细胞瘤的基因组改变影响脑脊液代谢产物的水平。
DOI：
10.1186/s40478-024-01722-1
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发表时间：
2024-01-19
影响因子：
7.1
通讯作者：
中科院分区：
文献类型：
--
作者：
脑脊液（CSF）分析在胶质母细胞瘤（GBM）患者中未得到充分利用，部分原因是缺乏证明CSF生物标志物临床效用的研究。虽然一些研究显示了CSF无细胞DNA分析的实用性，但分析胶质母细胞瘤患者CSF代谢物的研究有限。弥漫性神经胶质瘤改变了细胞代谢。例如，异柠檬酸脱氢酶中的突变（例如，IDH 1和IDH 2）常见于弥漫性神经胶质瘤，并导致CSF中D-2-羟基戊二酸水平升高。然而，对GBM患者CSF代谢物的变化了解甚少。在这项研究中，我们通过质谱法对来自n = 31名GBM患者和n = 13名非肿瘤性疾病患者（对照组）的CSF进行了靶向代谢组学分析。分层聚类和稀疏偏最小二乘判别分析（sPLS-DA）揭示了GBM和对照CSF之间CSF代谢物的差异，包括与脂肪酸氧化和肠道微生物组相关的代谢物（即，肉毒碱、2-甲基丁酰肉毒碱、莽草酸酯、氨基丁醛、尿苷、N-乙酰腐胺和法呢基二磷酸）。此外，我们根据TP 53或PTEN突变的存在/不存在，确定了GBM患者CSF代谢物的差异，这与不同突变对肿瘤代谢具有不同影响的观点一致。总之，我们的研究结果增加了对弥漫性胶质瘤患者CSF代谢物的理解，并突出了几种可能是GBM患者信息生物标志物的代谢物。在线版本包含补充材料，可通过10.1186/s40478-024-01722-1获得。
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. The online version contains supplementary material available at 10.1186/s40478-024-01722-1.
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影响因子：
4
作者：
Bark, Juliana Muller;Karpe, Avinash V.;Doecke, James D.;Leo, Paul;Jeffree, Rosalind L.;Chua, Benjamin;Day, Bryan W.;Beale, David J.;Punyadeera, Chamindie
通讯作者：
Punyadeera, Chamindie
影响因子：
2.3
作者：
Kampa, Judith M.;Kellner, Udo;Bednarz, Hanna
通讯作者：
Bednarz, Hanna
代谢组学方法揭示了肿瘤生物学的重要胶质母细胞瘤血浆生物标志物。
影响因子：
5.6
作者：
通讯作者：
--
影响因子：
2
作者：
Franceschi, Enrico;Tosoni, Alicia;Brandes, Alba A.
通讯作者：
Brandes, Alba A.
DOI：
10.1093/noajnl/vdac054
发表时间：
2022-01
期刊：
NEURO-ONCOLOGY ADVANCES
影响因子：
--
作者：
Dono, Antonio;Nickles, Jack;Rodriguez-Armendariz, Ana G.;McFarland, Braden C.;Ajami, Nadim J.;Ballester, Leomar Y.;Wargo, Jennifer A.;Esquenazi, Yoshua
通讯作者：
Esquenazi, Yoshua