NDLI: Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

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Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

Content Provider	MDPI
Author	Thomas, E. Mürdter Neef, Sylvia K. Janssen, Nicole Winter, Stefan Wallisch, Svenja K. Hofmann, Ute Dahlke, Marc H. Schwab, Matthias Haag, Mathias
Copyright Year	2020
Description	As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) facing the challenge of capturing metabolic information from a minimal sample amount (v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on the p-value and fold change cut-offs, which retained features with signal intensities >120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2′-deoxyuridine, 2′-O-methylcytidine, inosine and 1-methyladenosine and depletion of 2′-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.
Starting Page	494
e-ISSN	22181989
DOI	10.3390/metabo10120494
Journal	Metabolites
Issue Number	12
Volume Number	10
Language	English
Publisher	MDPI
Publisher Date	2020-12-01
Access Restriction	Open
Subject Keyword	Metabolites Biochemical Research Metabolomics Lipidomics Metabolic Profiling Organoids Colorectal Cancer Qtof Lc-ms
Content Type	Text
Resource Type	Article

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