Spatial differentiation of metabolism in prostate cancer tissue by MALDI-TOF MSI.
Spatial differentiation of metabolism in prostate cancer tissue by MALDI-TOF MSI.
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DOI：
10.1186/s40170-021-00242-z
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发表时间：
2021-01-29
影响因子：
5.9
通讯作者：
Tessem MB
中科院分区：
文献类型：
--
作者：
Andersen MK;Høiem TS;Claes BSR;Balluff B;Martin-Lorenzo M;Richardsen E;Krossa S;Bertilsson H;Heeren RMA;Rye MB;Giskeødegård GF;Bathen TF;Tessem MB
前列腺癌组织本质上是异质的，这对使用产生平均谱的传统批量分析方法进行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，这是一种促进异质组织切片的分子成像的方法，随后可以与同一切片的组织学相关。在这里，我们同时获得了代谢和lipidomic配置文件在不同的前列腺组织类型使用基质辅助激光解吸/电离飞行时间（MALDI-TOF）MSI。应用正离子和负离子模式分析来自45个新鲜冷冻的人前列腺组织样本（N = 15名患者）的连续切片。质量鉴定进行串联MS。成对比较癌症，非癌上皮细胞和间质揭示了几个组织类型之间的代谢差异。我们检测到癌症中对脂质代谢至关重要的代谢物水平增加，包括参与肉毒碱穿梭的代谢物，这有助于脂肪酸氧化，以及脂质合成所需的构建模块。与健康前列腺功能相关的代谢物，包括柠檬酸盐、天冬氨酸盐、锌和精胺，与非癌上皮相比，在癌症中的水平较低。间质的分析显示，与癌和非癌上皮相比，重要的能量代谢产物（如ADP、ATP和葡萄糖）水平较高，抗氧化剂牛磺酸水平较高。这项研究表明，前列腺癌样本中的特定组织区室具有不同的代谢谱，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作为临床有前途的创新诊断工具。在线版本包含补充材料，可通过10.1186/s40170-021-00242-z获得。
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. The online version contains supplementary material available at 10.1186/s40170-021-00242-z.
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DOI：
10.1073/pnas.1700677114
发表时间：
2017-03-28
影响因子：
11.1
作者：
Banerjee, Shibdas;Zare, Richard N.;Sonn, Geoffrey A.
通讯作者：
Sonn, Geoffrey A.
影响因子：
3.8
作者：
Dudka, Ilona;Thysell, Elin;Grobner, Gerhard
通讯作者：
Grobner, Gerhard
影响因子：
5
作者：
Morse, Nicole;Jamaspishvili, Tamara;Berman, David M.
通讯作者：
Berman, David M.
影响因子：
3.5
作者：
Marcinkiewicz J;Kontny E
通讯作者：
Kontny E
DOI：
10.1016/j.chemolab.2004.12.011
发表时间：
2005-07-28
影响因子：
3.9
作者：
Chong, IG;Jun, CH
通讯作者：
Jun, CH