Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section

Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section
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DOI:
10.1021/acs.analchem.6b01739
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发表时间:
2016-08-02
影响因子:
7.4
通讯作者:
McDonnell, Liam A.
McDonnell, Liam A.
中科院分区:
化学1区
文献类型:
--
作者:
Heijs, Bram;Holst, Stephanie;McDonnell, Liam A.

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组织消化基质辅助激光解吸/电离质谱成像 (MALDI-MSI) 可用于记录福尔马林固定石蜡包埋 (FFPE) 组织切片的空间相关分子信息。在这项工作中,我们对来自同一 FFPE 组织切片的 N 连接聚糖和蛋白质进行了原位多模态分析。该方法的稳健性和适用性已在多种肿瘤中得到证实,包括上皮和间质肿瘤类型。已针对 N-聚糖和蛋白水解肽研究了主要分析方面,例如分析物分子的横向扩散以及由于额外的样品制备方法而导致的测量灵敏度差异。通过将 MSI 方法与提取物分析相结合,我们还能够评估 MALDI-MSI 生成的哪些质谱峰可以分配给独特的 N-聚糖和肽身份。
On-tissue digestion matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can be used to record spatially correlated molecular information from formalin-fixed, paraffin-embedded (FFPE) tissue sections. In this work, we present the in situ multimodal analysis of N-linked glycans and proteins from the same FFPE tissue section. The robustness and applicability of the method are demonstrated for several tumors, including epithelial and mesenchymal tumor types. Major analytical aspects, such as lateral diffusion of the analyte molecules and differences in measurement sensitivity due to the additional sample preparation methods, have been investigated for both N-glycans and proteolytic peptides. By combining the MSI approach with extract analysis, we were also able to assess which mass spectral peaks generated by MALDI-MSI could be assigned to unique N-glycan and peptide identities.