Maria K Andersen1, Therese S Høiem2, Britt S R Claes3, Benjamin Balluff3, Marta Martin-Lorenzo3, Elin Richardsen4,5, Sebastian Krossa2, Helena Bertilsson6,7, Ron M A Heeren3, Morten B Rye6,8,9,10, Guro F Giskeødegård2, Tone F Bathen2, May-Britt Tessem11,12. 1. Department of Circulation and Medical Imaging, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. maria.k.andersen@ntnu.no. 2. Department of Circulation and Medical Imaging, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. 3. Maastricht MultiModal Molecular Imaging institute (M4I), Maastricht University, Maastricht, The Netherlands. 4. Department of Medical Biology, UiT The Artic University of Norway, Tromsø, Norway. 5. Department of Clinical Pathology, University Hospital of North Norway, UNN, Tromsø, Norway. 6. Department of Clinical and Molecular Medicine, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. 7. Department of Urology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 8. Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 9. Clinic of Laboratory Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 10. BioCore-Bioinformatics Core Facility, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. 11. Department of Circulation and Medical Imaging, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. may-britt.tessem@ntnu.no. 12. Clinic of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. may-britt.tessem@ntnu.no.
Abstract
BACKGROUND: Prostate cancer tissues are inherently heterogeneous, which presents a challenge for metabolic profiling using traditional bulk analysis methods that produce an averaged profile. The aim of this study was therefore to spatially detect metabolites and lipids on prostate tissue sections by using mass spectrometry imaging (MSI), a method that facilitates molecular imaging of heterogeneous tissue sections, which can subsequently be related to the histology of the same section. METHODS: Here, we simultaneously obtained metabolic and lipidomic profiles in different prostate tissue types using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MSI. Both positive and negative ion mode were applied to analyze consecutive sections from 45 fresh-frozen human prostate tissue samples (N = 15 patients). Mass identification was performed with tandem MS. RESULTS: Pairwise comparisons of cancer, non-cancer epithelium, and stroma revealed several metabolic differences between the tissue types. We detected increased levels of metabolites crucial for lipid metabolism in cancer, including metabolites involved in the carnitine shuttle, which facilitates fatty acid oxidation, and building blocks needed for lipid synthesis. Metabolites associated with healthy prostate functions, including citrate, aspartate, zinc, and spermine had lower levels in cancer compared to non-cancer epithelium. Profiling of stroma revealed higher levels of important energy metabolites, such as ADP, ATP, and glucose, and higher levels of the antioxidant taurine compared to cancer and non-cancer epithelium. CONCLUSIONS: This study shows that specific tissue compartments within prostate cancer samples have distinct metabolic profiles and pinpoint the advantage of methodology providing spatial information compared to bulk analysis. We identified several differential metabolites and lipids that have potential to be developed further as diagnostic and prognostic biomarkers for prostate cancer. Spatial and rapid detection of cancer-related analytes showcases MALDI-TOF MSI as a promising and innovative diagnostic tool for the clinic.
BACKGROUND:Prostate cancer tissues are inherently heterogeneous, which presents a challenge for metabolic profiling using traditional bulk analysis methods that produce an averaged profile. The aim of this study was therefore to spatially detect metabolites and lipids on prostate tissue sections by using mass spectrometry imaging (MSI), a method that facilitates molecular imaging of heterogeneous tissue sections, which can subsequently be related to the histology of the same section. METHODS: Here, we simultaneously obtained metabolic and lipidomic profiles in different prostate tissue types using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MSI. Both positive and negative ion mode were applied to analyze consecutive sections from 45 fresh-frozen human prostate tissue samples (N = 15 patients). Mass identification was performed with tandem MS. RESULTS: Pairwise comparisons of cancer, non-cancer epithelium, and stroma revealed several metabolic differences between the tissue types. We detected increased levels of metabolites crucial for lipid metabolism in cancer, including metabolites involved in the carnitine shuttle, which facilitates fatty acid oxidation, and building blocks needed for lipid synthesis. Metabolites associated with healthy prostate functions, including citrate, aspartate, zinc, and spermine had lower levels in cancer compared to non-cancer epithelium. Profiling of stroma revealed higher levels of important energy metabolites, such as ADP, ATP, and glucose, and higher levels of the antioxidant taurine compared to cancer and non-cancer epithelium. CONCLUSIONS: This study shows that specific tissue compartments within prostate cancer samples have distinct metabolic profiles and pinpoint the advantage of methodology providing spatial information compared to bulk analysis. We identified several differential metabolites and lipids that have potential to be developed further as diagnostic and prognostic biomarkers for prostate cancer. Spatial and rapid detection of cancer-related analytes showcases MALDI-TOF MSI as a promising and innovative diagnostic tool for the clinic.
Entities:
Keywords:
Mass spectrometry imaging; Metabolism; Prostate cancer; Tumor heterogeneity
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