Andersen Maria K, Høiem Therese S, Claes Britt S R, Balluff Benjamin, Martin-Lorenzo Marta, Richardsen Elin, Krossa Sebastian, Bertilsson Helena, Heeren Ron M A, Rye Morten B, Giskeødegård Guro F, Bathen Tone F, Tessem May-Britt
Department of Circulation and Medical Imaging, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
Maastricht MultiModal Molecular Imaging institute (M4I), Maastricht University, Maastricht, The Netherlands.
Cancer Metab. 2021 Jan 29;9(1):9. doi: 10.1186/s40170-021-00242-z.
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.
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.
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.
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.
前列腺癌组织本质上具有异质性，这给使用传统批量分析方法进行代谢谱分析带来了挑战，因为传统方法只能生成平均谱图。因此，本研究的目的是通过质谱成像（MSI）在前列腺组织切片上进行空间代谢物和脂质检测，该方法有助于对异质组织切片进行分子成像，随后可将其与同一切片的组织学相关联。
在此，我们使用基质辅助激光解吸/电离飞行时间（MALDI-TOF）MSI同时获得了不同前列腺组织类型的代谢和脂质组学谱图。采用正离子和负离子模式对45份新鲜冷冻的人类前列腺组织样本（N = 15例患者）的连续切片进行分析。通过串联质谱进行质量鉴定。
对癌组织、非癌上皮组织和基质进行两两比较，发现不同组织类型之间存在多种代谢差异。我们检测到癌组织中对脂质代谢至关重要的代谢物水平升高，包括参与肉碱穿梭的代谢物，肉碱穿梭有助于脂肪酸氧化，以及脂质合成所需的构建块。与非癌上皮组织相比，与健康前列腺功能相关的代谢物，如柠檬酸、天冬氨酸、锌和精胺，在癌组织中的水平较低。基质分析显示，与癌组织和非癌上皮组织相比，重要能量代谢物如二磷酸腺苷（ADP）、三磷酸腺苷（ATP）和葡萄糖的水平较高，抗氧化剂牛磺酸的水平也较高。
本研究表明，前列腺癌样本中的特定组织区域具有独特的代谢谱，并指出了与批量分析相比提供空间信息的方法的优势。我们鉴定了几种差异代谢物和脂质，它们有潜力进一步开发为前列腺癌的诊断和预后生物标志物。对癌症相关分析物的空间和快速检测表明，MALDI-TOF MSI是一种有前途的创新临床诊断工具。
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