Urinary metabolomic analysis of intrahepatic cholestasis of pregnancy based on high performance liquid chromatography/mass spectrometry
Urinary metabolomic analysis of intrahepatic cholestasis of pregnancy based on high performance liquid chromatography/mass spectrometry
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基于高效液相色谱/质谱法的妊娠期肝内胆汁淤积症尿液代谢组学分析
DOI：
10.1016/j.cca.2017.06.021
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发表时间：
2017-08-01
影响因子：
5
通讯作者：
Ding, Min
中科院分区：
文献类型：
--
作者：
Ma, Li;Zhang, Xiaoqing;Ding, Min
背景妊娠期肝内胆汁淤积症（ICP）是一种妊娠相关的肝脏疾病，可导致母亲和胎儿的并发症。代谢组学方法已应用于母胎医学。ICP的整体代谢组学改变是特异性的，但尚未被研究。方法：基于高效液相色谱/混合四极杆飞行时间采用高效液相色谱/飞行时间质谱（HPLC/Q TOF）联用技术，应用非靶向代谢组学方法分析ICP组与对照组尿代谢产物的变化。正向模型中有109个变量与负向模型中有119个变量差异显著ICP组与对照组比较差异有统计学意义（p < 0.05），正交偏最小二乘判别分析（OPLS-DA）显示VIP评分> 1。根据人类代谢物组数据库（human metabolome database，HMDB），筛选并鉴定了阳性模型中的14种代谢物和阴性模型中的18种代谢物。这些代谢产物主要参与胆汁酸的生物合成与代谢、激素代谢和脂质代谢。通过二元逻辑回归分析对比代谢物组（MG（22：5）、LysoPE（22：5）、L-同型半胱氨酸磺酸、甘氨胆酸和鹅去氧胆酸3-硫酸盐），对ICP具有高诊断准确性。受试者工作特征曲线下面积为0.988，敏感性为90.0%，特异性为93.3%。结论：尿代谢产物可用于ICP与对照组的判别分析。因此，这些发现可能为ICP的发病机制提供了深刻的见解。此外，母体尿代谢物组有可能用作ICP诊断的非侵入性生物标志物。
Background. Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-related liver disease, leads to complications for both mothers and fetuses. Metabolomic approach has been applied to maternal-fetal medicine. The global metabolomic alterations that are specific in ICP as yet have not been investigated.Methods: Based on high performance liquid chromatography/hybrid quadrupole time-of-flight (HPLC/Q TOF) mass spectrometry, the untargeted metabolomics was used to analyze the changes of urinary metabolites between ICP group and the control group.Results: One hundred nine variables in positive model and 119 variables in negative model were significantly different (p < 0.05) between the ICP group and the control group, with the VIP (variable importance in the project) score > 1 by the orthogonal partial least squares discriminant analysis (OPLS-DA). 14 metabolites in positive model and 18 metabolites in negative model were selected and identified based on HMDB (human metabolome database). Most of these metabolites were involved in bile acids biosynthesis and metabolism, hormone metabolism and lipid metabolism. A metabolite panel (MG (22:5), LysoPE (22:5), L-homocysteine sulfonic acid, glycocholic acid and chenodeoxycholic acid 3-sulfate) was contrusted by the binary logistic regression analysis with high diagnostic accuracy for ICP. The area under the receiver operating characteristic curve was 0.988 with the sensitivity of 90.0% and specificity of 93.3%.Conclusions: Urinary metabolites allow for the discrimination of ICP from the controls by orthogonal partial least squares discriminant analysis. Therefore, these findings may provide deep insights for the etiopathogenesis of ICP. Moreover, the maternal urinary metabolite panel has the potential to be used as non-invasive biomarkers for the diagnosis of ICP.