丙型肝炎病毒自发清除者的血清代谢组学研究

A metabonomics study of patients with spontaneous clearance of hepatitis C virus

目的探索HCV自发清除者、慢性丙型肝炎（丙肝）及健康人血清代谢组学的差异。方法纳入HCV自发清除者、慢性丙肝患者和健康对照各30例，采用快速液相色谱一串联质谱联用（LC—MS／MS）技术，应用主成分分析（PCA）、正交偏最小二乘法一判别分析（OPLS-DA）进行模式识别，然后通过变量重要性因子（VIP）、非参数检验，结合数据库检索筛选鉴定有差异的代谢物。结果25个变量被确认为存在显著差异的代谢物，其中7个变量被鉴定为花生四烯酸、棕榈油酸、葵酰基肉碱、溶血磷脂酰胆碱（20：5，16：0）、溶血磷脂酰乙醇胺（16：0，18：0），涉及脂肪酸、磷脂等代谢。其中花生四烯酸以及未鉴定出明确结构的m／z179．0719、m／z382．1360、m／z548．3475、m／z680．4281、m／z303．2323等物质与自发清除组的相关性较好，受试者工作特征曲线下面积为0．887-0．977，具有较好的特异度和敏感度。结论HCV自发清除者、慢性丙肝感染者、健康人在血清代谢水平上存在明显差异，这些差异的意义有待进一步探索。

Objective To explore the difference of serum metabonomics among patients with spontaneous clearance of hepatitis C virus （HCV）, patients with chronic hepatitis C （CHC） and healthy controls. Methods Thirty patients with spontaneous clearance of HCV, 30 patients with CHC and 30 healthy controls were enrolled in this study. Rapid liquid chromatography-tandem mass spectrometry （LC-MS/MS） and performed pattern recognition by principal component analysis （PCA） and orthogonal partial least squares discriminant analysis （OPLS-DA） in each group was applied. Then several metabolites which were different among the 3 groups through variable importance in projection （VIP） value, non-parametric test and screening in databases was identified. Results Twenty-five variables that were significantly different among the 3 groups were considered as potential biomarkers, among which 7 variables were identified as arachidonic acid, palmitoleic acid, dodecanoylcarnitine, lysophosphatidylcholine （ LysoPC [20：5 （5Z, 8Z, llZ, 14Z, 17Z）]}, LysoPC （16：0）, Lysophosphatidylethanolamine [LysoPE （18：0）], LysoPE （16：0）, all related to the metabolism of fatty acid and phospholipids. Especially, there was a good correlation between arachidonic acid as well as some other variables whose structures were not identified clearly, such as m/z 179. 0719, m/z382. 1360, m/z 548. 3475, m/z 680. 4281 and m/z 303. 2323, and patients with spontaneous clearance of HCV, with an area under the curve （AUC） from 0. 887 to 0. 977 and good specificity and sensitivity. Conclusion A marked difference of serum metabolic profiles exists among patients with spontaneous clearance of HCV, patients with CHC and healthy controls, and its clinical significance requires further study.