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Time-Resolved Metabolomics of a Mouse Model of High-Grade Serous Ovarian Cancer (MSI)

ABSTRACT: The dismally low survival rate of ovarian cancer patients diagnosed with high-grade serous carcinoma (HGSC) emphasizes the lack of effective screening strategies. One major obstacle is the limited knowledge of the underlying mechanisms of HGSC pathogenesis at very early stages. Here, we present the first 10-month time-resolved serum metabolic profile of a triple mutant (TKO) HGSC mouse model, along with the spatial lipidome profile of its entire reproductive system. A high-coverage liquid chromatography mass spectrometry-based metabolomics approach was applied to longitudinally collected serum samples from both TKO and TKO control mice, tracking metabolome and lipidome changes from disease onset until mouse death. Spatial lipid distributions within the reproductive system were also mapped via ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry and compared with serum lipid profiles for various lipid classes. Altogether, our results show that the remodeling of lipid and fatty acid metabolism, amino acid biosynthesis, TCA cycle and ovarian steroidogenesis are critical components of HGSC onset and development. These metabolic alterations are accompanied by changes in energy metabolism, mitochondrial and peroxisomal function, redox homeostasis, and inflammatory response, collectively supporting tumorigenesis.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Ovaries

DISEASE(S): Cancer

SUBMITTER: Samyukta Sah

PROVIDER: ST002083 | MetabolomicsWorkbench | Thu Feb 10 00:00:00 GMT 2022

REPOSITORIES: MetabolomicsWorkbench

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