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.

中文翻译：

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MALDI-TOF MSI在前列腺癌组织中代谢的空间分化

前列腺癌组织固有地是异质的，这对使用产生平均轮廓的传统本体分析方法的代谢谱分析提出了挑战。因此，本研究的目的是通过使用质谱成像（MSI）在空间上检测前列腺组织切片上的代谢物和脂质，该方法可促进异质组织切片的分子成像，随后可与同一切片的组织学相关。在这里，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特征。正离子和负离子模式均用于分析45份新鲜冷冻的人前列腺组织样本（N = 15例患者）的连续切片。使用串联MS进行质量鉴定。癌症，非癌症上皮和间质的成对比较显示了不同组织类型之间的几种代谢差异。我们检测到对于癌症中脂质代谢至关重要的代谢物水平升高，包括肉碱穿梭中涉及的代谢物，这有助于脂肪酸氧化，以及脂质合成所需的结构单元。与非前列腺癌上皮相比，与健康的前列腺功能相关的代谢产物（包括柠檬酸盐，天冬氨酸，锌和精胺）的癌症水平较低。与癌症和非癌症上皮相比，基质的分析显示较高水平的重要能量代谢物（例如ADP，ATP和葡萄糖）和较高水平的抗牛磺酸。这项研究表明，前列腺癌样本中的特定组织区室具有独特的代谢谱，并指出了与批量分析相比提供空间信息的方法的优势。我们确定了几种差异代谢物和脂质，它们有可能进一步发展为前列腺癌的诊断和预后生物标志物。癌症相关分析物的空间和快速检测展示了MALDI-TOF MSI是临床上一种有前途的创新诊断工具。