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靶向代谢谱分析在确定不同级别胶质瘤人类活检组织中的代谢异质性方面的应用

Targeted Metabolic Profiling in Determining the Metabolic Heterogeneity in Human Biopsies of Different Grades of Glioma.

作者信息

Vanisree Arambakkam Janardhanam, Thamizhoviya Gangadharan, Thiruvalluvan Arumugam

机构信息

Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.

Institute of Neurosurgery, Madras Medical College, Chennai, Tamil Nadu, India.

出版信息

Mol Neurobiol. 2025 Apr;62(4):4377-4390. doi: 10.1007/s12035-024-04538-1. Epub 2024 Oct 24.

Abstract

Gliomas are intricate tumors with numerous metabolic and genetic abnormalities contributing to their aggressive phenotypes and poor prognoses. The study aims at identifying the key molecular metabolic as well as gene expressional variations that could be used to differentiate between different grades of glioma to obtain deeper insights the about metabolic status of glioma that may serve as good candidates of diagnosis in future. In the present study, the metabolomic profiling along with clinical and expressional analyses of glioma biopsies (n = 52; patients comprising both of benign and malignant lesions) was analyzed. The biopsies were subjected to gene/protein expressional analysis using RT-PCR and western blotting and also were subjected to metabolite analyses. The results of the gene/protein expressional analysis exhibited elevated levels of carnitine palmitoyltransferase, monoglyceride lipase, human phosphofructokinase, and isocitrate dehydrogenase in higher grades of glioma when compared to those of control. Our study suggested that the metabolites and gene/protein expressional levels were found to be discriminative among the grades of glioma. The study is deemed as a provider of deeper insights that are essential for differential therapeutic approaches that specifically target the dysregulated metabolome to the benefit of patients.

摘要

神经胶质瘤是复杂的肿瘤,具有众多代谢和基因异常,导致其侵袭性表型和不良预后。该研究旨在确定关键的分子代谢以及基因表达变化,这些变化可用于区分不同级别的神经胶质瘤,以便更深入地了解神经胶质瘤的代谢状态,这些代谢状态未来可能成为良好的诊断候选指标。在本研究中,对神经胶质瘤活检样本(n = 52;包括良性和恶性病变患者)进行了代谢组学分析以及临床和表达分析。对活检样本进行了逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法的基因/蛋白质表达分析,还进行了代谢物分析。与对照组相比,基因/蛋白质表达分析结果显示,高级别神经胶质瘤中肉碱棕榈酰转移酶、甘油单酯脂肪酶、人磷酸果糖激酶和异柠檬酸脱氢酶的水平升高。我们的研究表明,代谢物以及基因/蛋白质表达水平在不同级别的神经胶质瘤之间具有鉴别性。该研究被认为提供了更深入的见解,这对于针对失调代谢组的特异性差异治疗方法至关重要,有利于患者。

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