Materials Characterization & Preparation Center, Southern University of Science and Technology, Shenzhen 518055, China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.
J Chromatogr A. 2019 Jan 4;1583:80-87. doi: 10.1016/j.chroma.2018.11.014. Epub 2018 Nov 11.
Modified metabolites play important roles in diagnostic monitoring, oxidative response and physiological regulation. Comprehensive analytical methods are greatly needed for improving the coverage of modified metabolites and studying their physiological function. Here, a novel nontargeted profiling method for mapping modified metabolites was developed by liquid chromatography-high resolution mass spectrometry with full scan/all ion fragmentation/neutral loss (FS/AIF/NL) data acquisition. Modified metabolites were unbiasedly defined with less false positive results by mixed standards verification. Thirteen types of modified metabolites in urine were analyzed at the same time, and 198 of 307 modified metabolites at positive mode and 166 of 366 modified metabolites at negative mode were putatively identified. The modified metabolites profiling method was applied for investigating the metabolic differences between the patients with breast cancer and health controls. As a result, many modified metabolites with glucuronidation, ribosylation and indole acetylation modification were significantly up-regulated in breast cancer and four modified metabolites including 7-methylguanosine, N-acetylcytidine, dihyroxy-1H-indole glucuronide I and indole-3-acetic acid-O-glucuronide were identified as potential biomarkers for the diagnose of breast cancer.
修饰代谢物在诊断监测、氧化反应和生理调节中起着重要作用。需要综合的分析方法来提高修饰代谢物的覆盖范围，并研究它们的生理功能。在这里，开发了一种新的非靶向代谢组学分析方法，用于通过液相色谱-高分辨质谱进行修饰代谢物的图谱分析，采用全扫描/所有离子碎裂/中性丢失（FS/AIF/NL）数据采集。通过混合标准品验证，修饰代谢物被无偏地定义，假阳性结果更少。同时分析了尿液中的 13 种修饰代谢物，正离子模式下鉴定出 307 种修饰代谢物中的 198 种，负离子模式下鉴定出 366 种修饰代谢物中的 166 种。该修饰代谢物图谱分析方法用于研究乳腺癌患者与健康对照者之间的代谢差异。结果表明，乳腺癌患者中许多具有葡萄糖醛酸化、核糖基化和吲哚乙酰化修饰的修饰代谢物显著上调，并且鉴定出 7-甲基鸟苷、N-乙酰胞苷、二羟基-1H-吲哚葡萄糖醛酸 I 和吲哚-3-乙酸-O-葡萄糖醛酸 4 种修饰代谢物作为乳腺癌诊断的潜在生物标志物。
