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- Title
Reproducible Lipid Alterations in Patient-Derived Breast Cancer Xenograft FFPE Tissue Identified with MALDI MSI for Pre-Clinical and Clinical Application.
- Authors
Denti, Vanna; Andersen, Maria K.; Smith, Andrew; Bofin, Anna Mary; Nordborg, Anna; Magni, Fulvio; Moestue, Siver Andreas; Giampà, Marco
- Abstract
The association between lipid metabolism and long-term outcomes is relevant for tumor diagnosis and therapy. Archival material such as formalin-fixed and paraffin embedded (FFPE) tissues is a highly valuable resource for this aim as it is linked to long-term clinical follow-up. Therefore, there is a need to develop robust methodologies able to detect lipids in FFPE material and correlate them with clinical outcomes. In this work, lipidic alterations were investigated in patient-derived xenograft of breast cancer by using a matrix-assisted laser desorption ionization mass spectrometry (MALDI MSI) based workflow that included antigen retrieval as a sample preparation step. We evaluated technical reproducibility, spatial metabolic differentiation within tissue compartments, and treatment response induced by a glutaminase inhibitor (CB-839). This protocol shows a good inter-day robustness (CV = 26 ± 12%). Several lipids could reliably distinguish necrotic and tumor regions across the technical replicates. Moreover, this protocol identified distinct alterations in the tissue lipidome of xenograft treated with glutaminase inhibitors. In conclusion, lipidic alterations in FFPE tissue of breast cancer xenograft observed in this study are a step-forward to a robust and reproducible MALDI-MSI based workflow for pre-clinical and clinical applications.
- Subjects
MATRIX-assisted laser desorption-ionization; DESORPTION ionization mass spectrometry; BREAST cancer; LIPIDS; LIPID metabolism; TREATMENT effectiveness; TISSUE differentiation
- Publication
Metabolites (2218-1989), 2021, Vol 11, Issue 9, p577
- ISSN
2218-1989
- Publication type
Article
- DOI
10.3390/metabo11090577