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一种用于全面分析具有不同突变的 GIST 异种移植物的多平台代谢组学方法。

A multiplatform metabolomics approach for comprehensive analysis of GIST xenografts with various mutations.

机构信息

Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.

Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, and Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.

出版信息

Analyst. 2023 Aug 7;148(16):3883-3891. doi: 10.1039/d3an00599b.

DOI:10.1039/d3an00599b
PMID:37458061
Abstract

Metabolites in biological matrices belong to diverse chemical groups, ranging from non-polar long-chain fatty acids to small polar molecules. The goal of untargeted metabolomic analysis is to measure the highest number of metabolites in the sample. Nevertheless, from an analytical point of view, no single technique can measure such a broad spectrum of analytes. Therefore, we selected a method based on GC-MS and LC-MS with two types of stationary phases for the untargeted profiling of gastrointestinal stromal tumours. The procedure was applied to GIST xenograft samples ( = 71) representing four different mutation models, half of which were treated with imatinib. We aimed to verify the method coverage and advantages of applying each technique. RP-LC-MS measured most metabolites due to a significant fraction of lipid components of the tumour tissue. What is unique and worth noting is that all applied techniques were able to distinguish between different mutation models. However, for detecting imatinib-induced alterations in the GIST metabolome, RP-LC-MS and GC-MS proved to be more relevant than HILIC-LC-MS, resulting in a higher number of significantly changed metabolites in four treated models. Undoubtedly, the inclusion of all mentioned techniques makes the method more comprehensive. Nonetheless, for green chemistry and time and labour saving, we assume that RP-LC-MS and GC-MS analyses are sufficient to cover the global GIST metabolome.

摘要

生物基质中的代谢物属于不同的化学基团,范围从非极性长链脂肪酸到小极性分子。非靶向代谢组学分析的目的是测量样品中最多的代谢物。然而,从分析的角度来看,没有一种单一的技术可以测量如此广泛的分析物。因此,我们选择了一种基于 GC-MS 和 LC-MS 与两种固定相的方法,用于非靶向 profiling 胃肠道间质瘤。该程序应用于代表四种不同突变模型的 GIST 异种移植样本(n = 71),其中一半用伊马替尼治疗。我们旨在验证该方法的覆盖范围和应用每种技术的优势。RP-LC-MS 测量了大多数代谢物,因为肿瘤组织中有很大一部分是脂质成分。值得注意的是,所有应用的技术都能够区分不同的突变模型。然而,对于检测伊马替尼诱导的 GIST 代谢组学变化,RP-LC-MS 和 GC-MS 比 HILIC-LC-MS 更相关,导致在四个治疗模型中有更多的代谢物发生显著变化。毫无疑问,包括所有提到的技术使方法更全面。然而,为了绿色化学和节省时间和劳动力,我们假设 RP-LC-MS 和 GC-MS 分析足以覆盖 GIST 的全局代谢组学。

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