基于同位素编码探针的LC-MS代谢轮廓分析新方法及其在肺癌标志物筛选中的应用

项目名称： 基于同位素编码探针的LC-MS代谢轮廓分析新方法及其在肺癌标志物筛选中的应用

项目编号： No.21305076

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 孙志伟

作者单位： 曲阜师范大学

项目金额： 25万元

中文摘要： LC-MS在诸多领域显示了强大能力，然而，在代谢轮廓分析方面仍存在缺陷。在非靶向分析方面，全面可靠地提取分析特征非常困难；在靶向分析方面，常受到基质效应的困扰。本项目以芳环并咪唑结构为母体，制备适用于胺基和羧基代谢物的14N/15N编码（及多重编码）分子探针，借助新型探针建立靶向和非靶向LC-MS代谢轮廓分析方法。在数据采集和预处理环节，充分利用同位素编码探针的辅助作用，提高LC-MS分析方法的性能，为后续多元统计分析提供高质量的数据。在非靶向分析过程中，发挥同位素辅助特征提取的作用，提取更多真正有意义的分析特征，提高发现生物标志物的概率；在靶向代谢轮廓分析过程中，发挥同位素内标定量的作用，克服基质效应的影响，提高方法的准确度和分析通量。将新方法应用于肺癌相关的胺类代谢谱和羧酸代谢谱的研究，发现或验证更多用于早期诊断、疗效评价和预后评估的代谢标志物，为提高肺癌的诊治水平提供理论基础。

中文关键词： 代谢组学；同位素编码标记；特征提取；内标定量；

英文摘要： Liquid chromatography-mass spectrometry (LC-MS) has become a powerful tool for clinical research, environmental science, and so on. However, its feasibility and reliabilities is seriously challenged in metabolic profile analysis. In the non-targeted analysis, it is very difficult to extract the comprehensive features from high resolution mass spectrometry data. In the targeted analysis, it often seriously suffers from matrix effect, reducing the typical advantages of mass spectrometric detection in terms of selectivity and specificity. The development of simple and effective way to overcome these problems is of great significance to the LC-MS based metabolomics studies. In this project, we will develop series of novel isotope-coded probes (also kown as isotope-coded derivatization reagents) for amines and carboxylic acids. These probes are designed by incorporating 14N/15N coding or multiple isotopic coding into the aromatic fused imidazole structure. With the aid of these new probes, the isotope-assisted non-targeted and targeted LC-MS metabolic profile analysis method will be developed. The performance of LC-MS metabolic file analysis can be drastically improved by making full use of the advantages of isotope-coded probes during the data acquisition and preprocessing, which is favorable to providing the high

英文关键词： Metabonomics；Isotope-coded labeling；Feature extraction；Internal standard quantity analysis；