基于气相色谱-质谱联用技术的乙型肝炎血清代谢标志物的探究  

Exploration on serum metabolic biomarkers of hepatitis B virus infected patients based on gas chromatography-mass spectrometry

作　　者：侯玉洁[1] 祝文君[2] 陈长功[1] 王彦[1] 段志军[3] 阎超[1] 

机构地区：[1]上海交通大学药学院,上海200240 [2]大连医科大学肿瘤干细胞研究院,辽宁大连116044 [3]大连医科大学附属第一医院,辽宁大连116011

出　　处：《色谱》2015年第4期383-388,共6页Chinese Journal of Chromatography

基　　金：国家自然科学基金项目(21175092;21105064);国家重大科学仪器设备开发专项(2011YQ150072;2011YQ15007204;2011YQ15007207;2011YQ15007210);上海市自然科学基金项目(12ZR1413600)

摘　　要：探索了乙型肝炎患者和健康人血清代谢组的差异,寻找与疾病相关的潜在标志物。收集乙肝患者30例、健康对照35例,以气相色谱-质谱联用技术作为研究平台,应用主成分分析、正交偏最小二乘法-判别分析进行模式识别,然后通过变量重要性因子、非参数检验,结合数据库检索筛选鉴定有差异的代谢物。确认10个代谢物存在显著差异,其中柠檬酸、乌头酸、谷氨酰胺、N,N-二甲基甘氨酸、丙二酸与乙型肝炎患者组的相关性较好,受试者工作特征曲线下面积为0.975,具有较好的特异度和敏感度。因此这5个代谢物能够作为潜在的区分乙型肝炎患者和正常人的血清小分子标志物,有助于进一步了解病理机制,确定治疗目标。The difference of serum metabolome between hepatitis B virus （ HBV ） infected patients and healthy controls was explored for the potential metabolite biomarkers of HBV dis.ease using serum metabolomics approach. Totally 30 HBV infected patients and 35 healthy con.trols were enrolled. Gas chromatography.time.of.flight mass spectrometry （ GC.TOFMS） , pat.tern recognition by principal component analysis （ PCA ） and orthogonal partial least squares.discriminant analysis （ OPLS.DA） were applied in each group. Several metabolites which were different between the two groups based on variable importance in projection （ VIP） value, non.parametric test and screening in databases were identified. Ten variables that were significantly different were considered as the potential biomarkers, among which five variables （ citric acid, aconitic acid, glutamine, N,N.dimethylglycine and malonic acid） showed good correlation with HBV patients. The area under the receiver operating characteristic curve was 0.975, with good specificity and sensitivity. A panel of metabolite markers composed of citric acid, aconitic acid, glutamine, N,N.dimethylglycine and malonic acid from GC.TOFMS were selected to discrimi.nate HBV subjects from their healthy counterparts. These biochemical changes provide a novel molecular diagnostic approach which could be helpful to further understand the pathogenesis and identify the therapeutic target of HBV disease.

关 键 词：气相色谱-质谱联用 正交偏最小二乘法-判别分析 潜在标志物 乙型肝炎 代谢组学 

分 类 号：O658[理学—分析化学]