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.