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非靶向代谢组学分析利用超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF/MS)的质谱模式描绘了肺癌发生过程中小鼠血浆中的代谢变化。

Untargeted metabolomics profiles delineate metabolic alterations in mouse plasma during lung carcinoma development using UPLC-QTOF/MS in MS mode.

作者信息

Wu Huan, Chen Yang, Li Zegeng, Liu Xianhua

机构信息

Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230038, People's Republic of China.

Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei 230012, People's Republic of China.

出版信息

R Soc Open Sci. 2018 Sep 19;5(9):181143. doi: 10.1098/rsos.181143. eCollection 2018 Sep.

Abstract

In this work, an untargeted metabolomic method based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) in MS (E represents collision energy) mode was exploited to determine the dynamic metabolic alterations in the plasma of male C57BL/6 mice during the onset and development of lung carcinoma. Plasma samples were collected from control and model mice (male C57BL/6 mice experimentally inoculated with the lung carcinoma cells) at 7 and 14 days post-inoculation (DPI). As a result, 15 dysregulated metabolites, including cholesterol sulphate, tiglylcarnitine, 1-palmitoylglycerophosphoinositol, 2-stearoylglycerophosphoinositol, stearoylcarnitine, PC(20:2(11Z,14Z)/16:0), PC(22:4(7Z,10Z,13Z,16Z)/14:0), PC(22:5(7Z,10Z,13Z,16Z,19Z)/14:0), PC(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:0), 12,20-Dioxo-leukotriene B4, sphingosine 1-phosphate(d19:1-P), sphingomyelin(d18:0/16:1(9Z)), lysoPC(16:0), lysoPC(18:0) and lysoPC(20:4(5Z,8Z,11Z,14Z)), were identified in the plasma of model mice with xenografts at both 7 and 14 DPI. All the altered metabolites associated with the onset and development of lung carcinoma were involved in the metabolism of glycerophospholipid, fatty acid, sphingolipid and arachidonic acid. The feasible utility of these endogenous biomarkers as potential diagnostic indicators was validated through receiver operating characteristic curve analysis. Collectively, these findings provide a systematic view of metabolic changes linked to the onset and development of lung carcinoma.

摘要

在本研究中,采用基于超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF/MS)的非靶向代谢组学方法,在MS(E代表碰撞能量)模式下测定雄性C57BL/6小鼠肺癌发生和发展过程中血浆的动态代谢变化。在接种后7天和14天(DPI)从对照小鼠和模型小鼠(经实验接种肺癌细胞的雄性C57BL/6小鼠)采集血浆样本。结果,在接种异种移植物的模型小鼠血浆中,在7和14 DPI时均鉴定出15种失调代谢物,包括硫酸胆固醇、惕格肉碱、1-棕榈酰甘油磷酸肌醇、2-硬脂酰甘油磷酸肌醇、硬脂酰肉碱、PC(20:2(11Z,14Z)/16:0)、PC(22:4(7Z,10Z,13Z,16Z)/14:0)、PC(22:5(7Z,10Z,13Z,16Z,19Z)/14:0)、PC(22:6(4Z,7Z,10Z,13Z,16Z,19Z)/16:0)、12,20-二氧白三烯B4、鞘氨醇1-磷酸(d19:1-P)、鞘磷脂(d18:0/16:1(9Z))、溶血磷脂酰胆碱(16:0)、溶血磷脂酰胆碱(18:0)和溶血磷脂酰胆碱(20:4(5Z,8Z,11Z,14Z))。所有与肺癌发生和发展相关的改变代谢物均参与甘油磷脂、脂肪酸、鞘脂和花生四烯酸的代谢。通过受试者工作特征曲线分析验证了这些内源性生物标志物作为潜在诊断指标的可行性。总的来说,这些发现提供了与肺癌发生和发展相关的代谢变化的系统观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b05/6170569/2b311f996259/rsos181143-g1.jpg

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