Department of Chemistry, Indiana University , Bloomington, Indiana 47405, United States.
J Proteome Res. 2012 Feb 3;11(2):576-85. doi: 10.1021/pr200777u. Epub 2011 Dec 30.
Altered branching and aberrant expression of N-linked glycans is known to be associated with disease states such as cancer. However, the complexity of determining such variations hinders the development of specific glycomic approaches for assessing disease states. Here, we examine a combination of ion mobility spectrometry (IMS) and mass spectrometry (MS) measurements, with principal component analysis (PCA) for characterizing serum N-linked glycans from 81 individuals: 28 with cirrhosis of the liver, 25 with liver cancer, and 28 apparently healthy. Supervised PCA of combined ion-mobility profiles for several, to as many as 10 different mass-to-charge ratios for glycan ions, improves the delineation of diseased states. This extends an earlier study [J. Proteome Res.2008, 7, 1109-1117] of isomers associated with a single glycan (S(1)H(5)N(4)) in which PCA analysis of the IMS profiles appeared to differentiate the liver cancer group from the other samples. Although performed on a limited number of test subjects, the combination of IMS-MS for different combinations of ions and multivariate PCA analysis shows promise for characterizing disease states.
糖基化修饰的分支结构和异常表达与疾病状态有关，例如癌症。然而，确定这些变化的复杂性阻碍了特定糖组学方法在评估疾病状态方面的发展。在这里，我们研究了离子淌度谱（IMS）和质谱（MS）测量的组合，以及主成分分析（PCA），以分析 81 个人的血清 N-连接聚糖：28 例肝硬化，25 例肝癌和 28 例健康人。对多种至多达 10 种不同质荷比的糖离子的离子淌度图谱进行联合的 PCA 监督分析，可改善疾病状态的划分。这扩展了先前研究[J. Proteome Res.2008, 7, 1109-1117]的一个结果，即与单个聚糖（S(1)H(5)N(4))相关的异构体，其中 IMS 图谱的 PCA 分析似乎可以将肝癌组与其他样本区分开来。尽管在有限数量的测试对象上进行，但 IMS-MS 与不同离子组合的结合以及多元 PCA 分析显示出了用于表征疾病状态的潜力。
