Sequential Orbitrap Secondary Ion Mass Spectrometry and Liquid Extraction Surface Analysis-Tandem Mass Spectrometry-Based Metabolomics for Prediction of Brain Tumor Relapse from Sample-Limited Primary Tissue Archives

Meurs, Joris; Scurr, David J.; Lourdusamy, Anbarasu; Storer, Lisa C.D.; Grundy, Richard G.; Alexander, Morgan R.; Rahman, Ruman; Kim, Dong-Hyun

Abstract

We present here a novel surface mass spectrometry strategy to perform untargeted metabolite profiling of formalin-fixed paraffin-embedded pediatric ependymoma archives. Sequential Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) and liquid extraction surface analysis-tandem mass spectrometry (LESA-MS/MS) permitted the detection of 887 metabolites (163 chemical classes) from pediatric ependymoma tumor tissue microarrays (diameter: <1 mm; thickness: 4 μm). From these 163 classes, 60 classes were detected with both techniques, whilst LESA-MS/MS and 3D OrbiSIMS individually allowed the detection of another 83 and 20 unique metabolite classes, respectively. Through data fusion and multivariate analysis, we were able to identify key metabolites and corresponding pathways predictive of tumor relapse, which were retrospectively confirmed by gene expression analysis with publicly available data. Altogether, this sequential mass spectrometry strategy has shown to be a versatile tool to perform high-throughput metabolite profiling on sample-limited tissue archives.

Citation

Meurs, J., Scurr, D. J., Lourdusamy, A., Storer, L. C., Grundy, R. G., Alexander, M. R., Rahman, R., & Kim, D.-H. (2021). Sequential Orbitrap Secondary Ion Mass Spectrometry and Liquid Extraction Surface Analysis-Tandem Mass Spectrometry-Based Metabolomics for Prediction of Brain Tumor Relapse from Sample-Limited Primary Tissue Archives. Analytical Chemistry, 93(18), 6947-6954. https://doi.org/10.1021/acs.analchem.0c05087

• Journal Article Type: Article
• Acceptance Date: Mar 25, 2021
• Online Publication Date: Apr 26, 2021
• Publication Date: May 11, 2021
• Deposit Date: Apr 16, 2021
• Publicly Available Date: Apr 27, 2022
• Journal: Analytical Chemistry
• Print ISSN: 0003-2700
• Electronic ISSN: 1520-6882
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 93
• Issue: 18
• Pages: 6947-6954
• DOI: https://doi.org/10.1021/acs.analchem.0c05087
• Keywords: Analytical Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/5468987
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.analchem.0c05087