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Sequential 3D OrbiSIMS and LESA-MS/MS-based metabolomics for prediction of brain tumor relapse from sample-limited primary tissue archives
bioRxiv - Cancer Biology Pub Date : 2021-03-25 , DOI: 10.1101/2020.07.15.182071
Joris Meurs , David J. Scurr , Lisa C.D. Storer , Richard G. Grundy , Morgan R. Alexander , Ruman Rahman , Dong-Hyun Kim

Ependymomas are the third most common brain tumor in children and are characterized by a high probability of relapse (>50%) and poor survival rate (<50%). The availability of pediatric ependymoma tissue for analysis is however scarce and small in size (<1 mm) limiting extensive metabolomics analysis into brain tumor metabolism using standard techniques such as gas or liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Here, we present a novel serial surface mass spectrometry-based strategy for metabolite profiling of pediatric ependymoma tissue microarrays (TMA) using Orbitrap secondary ion mass spectrometry (3D OrbiSIMS), followed by liquid extraction surface analysis-tandem MS (LESA-MS/MS). The use of this strategy permitted a broader coverage of metabolites and allowed identification of putative metabolites for accurate prediction of ependymoma relapse. This strategy opens new opportunities to retrospectively link molecular data from any formalin-fixed paraffin-embedded (FFPE) TMA library with clinical outcomes.

中文翻译:

顺序3D OrbiSIMS和基于LESA-MS / MS的代谢组学可从样品有限的主要组织档案中预测脑肿瘤的复发

室间隔膜瘤是儿童中第三大最常见的脑肿瘤,其特征是复发的可能性高(> 50%),生存率低(<50%)。然而,用于分析的儿科室膜膜瘤组织稀缺且尺寸小(<1 mm),限制了使用标准技术(例如气相色谱或液相色谱-质谱法和核磁共振波谱法)将广泛的代谢组学分析应用于脑肿瘤代谢。在这里,我们介绍一种基于串行表面质谱的新型策略,用于使用Orbitrap二次离子质谱仪(3D OrbiSIMS)对小儿室管膜瘤组织微阵列(TMA)进行代谢物分析,然后进行液相萃取串联质谱(LESA-MS / MS) )。该策略的使用允许更广泛的代谢物覆盖范围,并允许鉴定假定的代谢物以准确预测室间隔膜瘤的复发。该策略为将任何福尔马林固定石蜡包埋(FFPE)TMA库中的分子数据与临床结果进行回顾性链接提供了新的机会。
更新日期:2021-03-25
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