Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, P. R. China.
University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Analyst. 2024 Oct 7;149(20):5063-5072. doi: 10.1039/d4an00751d.
Aberrant lipid metabolism has been widely recognized as a hallmark of various diseases. However, the comprehensive analysis of distinct lipids is challenging due to the complexity of lipid molecular structures, wide concentration ranges, and numerous isobaric and isomeric lipids. Usually, liquid chromatography-mass spectrometry (LC-MS)-based lipidomics requires a long time for chromatographic separation to achieve optimal separation and selectivity. Ion mobility (IM) adds a new separation dimension to LC-MS, significantly enhancing the coverage, sensitivity, and resolving power. We took advantage of the rapid separation provided by ion mobility and optimized a fast and broad-coverage lipidomics method using the LC-IM-MS technology. The method required only 8 minutes for separation and detected over 1000 lipid molecules in a single analysis of common biological samples. The high reproducibility and accurate quantification of this high-throughput lipidomics method were systematically characterized. We then applied the method to comprehensively measure dysregulated lipid metabolism in patients with colorectal cancer (CRC). Our results revealed 115 significantly changed lipid species between preoperative and postoperative plasma of patients with CRC and also disclosed associated differences in lipid classes such as phosphatidylcholines (PC), sphingomyelins (SM), and triglycerides (TG) regarding carbon number and double bond. Together, a fast and broad-coverage lipidomics method was developed using ion mobility-mass spectrometry. This method is feasible for large-scale clinical lipidomic studies, as it effectively balances the requirements of high-throughput and broad-coverage in clinical studies.
异常的脂质代谢已被广泛认为是各种疾病的标志。然而，由于脂质分子结构的复杂性、广泛的浓度范围以及众多的同量异位和同构脂质，对不同脂质进行全面分析具有挑战性。通常，基于液相色谱-质谱（LC-MS）的脂质组学需要很长的色谱分离时间才能达到最佳的分离和选择性。离子淌度（IM）为 LC-MS 增加了一个新的分离维度，显著提高了覆盖度、灵敏度和分辨率。我们利用离子淌度提供的快速分离优势，并利用 LC-IM-MS 技术优化了一种快速、宽覆盖的脂质组学方法。该方法仅需 8 分钟即可完成分离，可在单个常见生物样本分析中检测到 1000 多种脂质分子。该高通量脂质组学方法具有很高的重现性和准确的定量特性，我们对其进行了系统表征。然后，我们将该方法应用于全面测量结直肠癌（CRC）患者失调的脂质代谢。我们的结果揭示了 CRC 患者术前和术后血浆之间有 115 种显著变化的脂质种类，并且还揭示了与碳数和双键相关的磷脂酰胆碱（PC）、鞘磷脂（SM）和甘油三酯（TG）等脂质种类的差异。总之，我们开发了一种使用离子淌度-质谱的快速、宽覆盖的脂质组学方法。该方法可用于大规模的临床脂质组学研究，因为它有效地平衡了高通量和宽覆盖在临床研究中的要求。
