دورية أكاديمية
أعرض في EDS

Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS.

التفاصيل البيبلوغرافية
العنوان: Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS.
المؤلفون: He W; Centre for Analytical Bioscience, Advanced Materials & Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K., Edney MK; Department of Chemical and Environmental Engineering, Faculty of Engineering, University of Nottingham, Nottingham NG7 7RD, U.K., Paine SML; Neuropathology Laboratory, Nottingham University Hospitals NHS Trust, Nottingham NG7 2UH, U.K., Griffiths RL; Centre for Analytical Bioscience, Advanced Materials & Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K., Scurr DJ; Centre for Analytical Bioscience, Advanced Materials & Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K., Rahman R; Children's Brain Tumour Research Centre, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham NG7 2RD, U.K., Kim DH; Centre for Analytical Bioscience, Advanced Materials & Healthcare Technologies Division, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K.
المصدر: Analytical chemistry [Anal Chem] 2023 Apr 11; Vol. 95 (14), pp. 5994-6001. Date of Electronic Publication: 2023 Mar 30.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370536 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6882 (Electronic) Linking ISSN: 00032700 NLM ISO Abbreviation: Anal Chem Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, American Chemical Society.
مواضيع طبية MeSH: Brain Neoplasms*/pathology , Glioblastoma*/pathology, Humans ; Prognosis ; Spectrometry, Mass, Secondary Ion ; Tumor Microenvironment ; Metabolomics
مستخلص: Glioblastoma (GBM) is an incurable brain cancer with a median survival of less than two years from diagnosis. The standard treatment of GBM is multimodality therapy comprising surgical resection, radiation, and chemotherapy. However, prognosis remains poor, and there is an urgent need for effective anticancer drugs. Since different regions of a single GBM contain multiple cancer subpopulations ("intra-tumor heterogeneity"), this likely accounts for therapy failure as certain cancer cells can escape from immune surveillance and therapeutic threats. Here, we present metabolomic data generated using the Orbitrap secondary ion mass spectrometry (OrbiSIMS) technique to investigate brain tumor metabolism within its highly heterogeneous tumor microenvironment. Our results demonstrate that an OrbiSIMS-based untargeted metabolomics method was able to discriminate morphologically distinct regions (viable, necrotic, and non-cancerous) within single tumors from formalin-fixed paraffin-embedded tissue archives. Specifically, cancer cells from necrotic regions were separated from viable GBM cells based on a set of metabolites including cytosine, phosphate, purine, xanthine, and 8-hydroxy-7-methylguanine. Moreover, we mapped ubiquitous metabolites across necrotic and viable regions into metabolic pathways, which allowed for the discovery of tryptophan metabolism that was likely essential for GBM cellular survival. In summary, this study first demonstrated the capability of OrbiSIMS for in situ investigation of GBM intra-tumor heterogeneity, and the acquired information can potentially help improve our understanding of cancer metabolism and develop new therapies that can effectively target multiple subpopulations within a tumor.
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تواريخ الأحداث: Date Created: 20230330 Date Completed: 20230412 Latest Revision: 20230417
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10100400
DOI: 10.1021/acs.analchem.2c05807
PMID: 36995369
قاعدة البيانات: MEDLINE
الوصف
تدمد:1520-6882
DOI:10.1021/acs.analchem.2c05807