University of Victoria-Genome British Columbia Proteomics Centre, Vancouver Island Technology Park, #3101-4464 Markham St., Victoria, BC V8Z 7X8, Canada.
University of Victoria-Genome British Columbia Proteomics Centre, Vancouver Island Technology Park, #3101-4464 Markham St., Victoria, BC V8Z 7X8, Canada; Department of Biochemistry and Microbiology, University of Victoria, Petch Building Room 207, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada.
Biochim Biophys Acta Proteins Proteom. 2017 Jul;1865(7):755-767. doi: 10.1016/j.bbapap.2016.12.012. Epub 2016 Dec 23.
In this work, we combined the use of two MALDI matrices (quercetin and 9-aminoacridine), a recently developed new matrix coating technique - matrix coating assisted by an electric field (MCAEF), and matrix-assisted laser desorption/ionization - Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICRMS) to detect and image endogenous compounds in the cancerous and non-cancerous regions of three human prostate cancer (stage II) tissue specimens. After three rounds of imaging data acquisitions (i.e., quercetin for positive and negative ion detection and 9-aminoacridine for negative ion detection), and metabolite identification, a total of 1091 metabolites including 1032 lipids and 59 other metabolites were routinely detected and successfully localized. Of these compounds, 250 and 217 were only detected in either the cancerous or the non-cancerous regions respectively, although we cannot rule out the presence of these metabolites at concentrations below the detection limit. In addition, 152 of the other 624 metabolites showed differential distributions (p<0.05, t-test) between the two regions of the tissues. Further studies on a larger number of clinical specimens will need to be carried out to confirm this large number of apparently cancer-related metabolites. The successful determination of the spatial locations and abundances of these endogenous biomolecules indicated significant metabolism abnormalities - e.g., increased energy charge and under-expression of neutral acyl glycerides, in the prostate cancer samples. To our knowledge, this work has resulted in MALDI-MS imaging of the largest group of metabolites in prostate cancer thus far and demonstrated the importance of using complementary matrices for comprehensive metabolomic imaging by MALDI-MS. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
在这项工作中，我们结合使用了两种 MALDI 基质（槲皮素和 9-氨基吖啶）、一种新的基质涂敷技术——电场辅助基质涂敷（MCAEF），以及基质辅助激光解吸/电离-傅里叶变换离子回旋共振质谱（MALDI-FTICRMS），以检测和成像三个人类前列腺癌（II 期）组织标本的癌性和非癌性区域中的内源性化合物。经过三轮成像数据采集（即，使用槲皮素进行正、负离子检测，使用 9-氨基吖啶进行负离子检测）和代谢物鉴定，共检测和成功定位了 1091 种代谢物，包括 1032 种脂质和 59 种其他代谢物。在这些化合物中，有 250 种和 217 种分别仅在癌性或非癌性区域中被检测到，尽管我们不能排除这些代谢物在低于检测限的浓度下存在的可能性。此外，其余 624 种代谢物中的 152 种在组织的两个区域之间表现出不同的分布（p<0.05，t 检验）。需要对更多的临床标本进行进一步研究，以证实这些大量与癌症相关的代谢物的存在。这些内源性生物分子的空间位置和丰度的成功确定表明，前列腺癌样本中存在显著的代谢异常，例如能量电荷增加和中性酰基甘油的表达下调。据我们所知，这项工作已经实现了迄今为止对前列腺癌中最大一组代谢物的 MALDI-MS 成像，并证明了使用互补基质对 MALDI-MS 进行全面代谢组学成像的重要性。本文是由 Corinna Henkel 博士和 Peter Hoffmann 教授编辑的特刊“MALDI 成像”的一部分。
