色谱

色谱 ›› 2015, Vol. 33 ›› Issue (4): 383-388.DOI: 10.3724/SP.J.1123.2014.12007

• 研究论文 • 上一篇    下一篇

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

侯玉洁1, 祝文君2, 陈长功1, 王彦1, 段志军3, 阎超1   

  1. 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
  • 收稿日期:2014-12-03 修回日期:2015-01-05 出版日期:2015-04-08 发布日期:2015-03-30
  • 通讯作者: 王彦, 段志军, 阎超
  • 基金资助:

    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).

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

HOU Yujie1, ZHU Wenjun2, CHEN Changgong1, WANG Yan1, DUAN Zhijun3, YAN Chao1   

  1. 1. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China;
    2. Institute of Cancer Stem Cell, Dalian Medical University, Dalian 116044, China;
    3. The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
  • Received:2014-12-03 Revised:2015-01-05 Online:2015-04-08 Published:2015-03-30

PDF

385

被引次数

11

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。

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

Abstract:

The difference of serum metabolome between hepatitis B virus (HBV) infected patients and healthy controls was explored for the potential metabolite biomarkers of HBV disease using serum metabolomics approach. Totally 30 HBV infected patients and 35 healthy controls were enrolled. Gas chromatography-time-of-flight mass spectrometry (GC-TOFMS), pattern 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 discriminate 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.

Key words: gas chromatography-mass spectrometry (GC-MS), hepatitis B virus (HBV), metabolomics, orthogonal partial least squares-discriminant analysis (OPLS-DA), potential biomarkers

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