Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry
Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry
复制标题
使用直接输注电喷雾电离傅里叶变换离子回旋共振质谱法进行脂质分析，用于结直肠癌的早期诊断和进展
DOI：
10.1002/rcm.6420
复制
发表时间：
2013-01-15
影响因子：
2
通讯作者：
Li, Zhili
中科院分区：
文献类型：
--
作者：
Li, Fang;Qin, Xuzhen;Li, Zhili
结直肠癌（CRC）由于其常见的发病率和全球分布而引起越来越多的关注。方法采用正、负离子直接注入电喷雾傅立叶变换离子回旋共振质谱（DI-ESI（+/-）-FTICR MS）技术，对52例结直肠癌患者和52例健康对照者的血清代谢产物进行分析。通过单变量和多变量统计分析确定组间强度具有统计学显著性的代谢物，通过人体代谢组数据库、精确质量测量、同位素丰度分布模拟和串联质谱法的组合进一步鉴定。正交偏最小二乘判别分析（OPLS-DA）的基础上的数据从DI-ESI（+/-）-FTICR MS，显示了显着的区分早期患者，晚期患者和健康对照。结果共鉴定出15种差异表达的代谢物，并将其分为4类。每种脂质类别在CRC进展中表现出特定的变化趋势。含有棕榈酰胺、油酰胺、十六烷二酸、十八烷酸、二十碳三烯酸、LPC（18：2）、LPC（20：4）、LPC（22：6）、肉豆蔻酸和LPC（16：0）的生物标志物组1实现了优异的诊断准确性，ROC曲线下面积（AUC）为0.991，区分早期患者与健康对照的灵敏度为0.981，特异性为1.000，其优于癌胚抗原生物标志物。结论我们的研究表明，在诊断生物标志物发现中需要考虑CRC分期，并且应注意[M？+？Cl]形式的LPC（16：0）。版权所有（c）2012约翰威利父子有限公司
RATIONALE Colorectal cancer (CRC) has attracted increasing attention due to its common occurrence and worldwide distribution. METHODS Direct-infusion positive and negative ion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (DI-ESI(+/-)-FTICR MS) was applied to analyze the serum metabolites from 52 CRC patients and 52 healthy controls. Metabolites whose inter-group intensities were determined to be statistically significant by univariate and multivariate statistical analyses were further identified by a combination of the Human Metabolome Database, accurate mass measurement, isotopic abundance distribution simulation, and tandem mass spectrometry. Orthogonal partial least square discriminant analysis (OPLS-DA), based on the data from DI-ESI(+/-)-FTICR MS, revealed a remarkable discrimination among early stage patients, late stage patients, and healthy controls. RESULTS A total of 15 differentially expressed metabolites were identified and categorized into four lipid classes. Each lipid class demonstrated specific changing trends in CRC progression. Biomarker panel 1 containing palmitic amide, oleamide, hexadecanedioic acid, octadecanoic acid, eicosatrienoic acid, LPC(18:2), LPC(20:4), LPC(22:6), myristic acid and LPC(16:0) achieved excellent diagnostic accuracy with area under the ROC curve (AUC) of 0.991, a sensitivity of 0.981 and a specificity of 1.000 for differentiating early stage patients from healthy controls, which was better than the carcinoembryonic antigen biomarker. CONCLUSIONS Our study revealed that the consideration of CRC stages would be necessary in diagnostic biomarker discovery, as well as that attention should be paid to the facile loss of methyl chloride from the [M?+?Cl] form of LPC(16:0) in its tandem mass spectrum. Copyright (c) 2012 John Wiley & Sons, Ltd.