Serum proteomic MRM identify peptide ions of transferrin as new fibrosis markers in chronic hepatitis B.
Serum proteomic MRM identify peptide ions of transferrin as new fibrosis markers in chronic hepatitis B.
复制标题
血清蛋白质组 MRM 将转铁蛋白肽离子识别为慢性乙型肝炎的新纤维化标志物。
DOI：
10.1016/j.biopha.2013.03.021
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Lungen Lu
中科院分区：
文献类型：
--
作者：
Mingyi Xu;Y. Qu;Xiaofang Jia;Mei;Heng Liu;Xing;Li;Lungen Lu
背景和目的由于肝活检的局限性，需要可靠的非侵入性肝纤维化血清标志物。本研究的目的是通过使用血清蛋白质组学在慢性B肝炎（CHB）中鉴定这些标志物。方法采用双向凝胶电泳（2-DE）技术鉴定40例CHB患者血清中差异表达的蛋白质点[20例轻度纤维化（S 0-S1）和20例重度纤维化（S3-S4）]。采用质谱多反应监测（MRM）技术对86例慢性乙型肝炎患者血清中不同肝纤维化程度（S 0 ~ S4）的差异蛋白质点进行肽离子定量分析。通过基于MS的MRM定量了7个靶蛋白点的14个肽离子。来自蛋白质斑点1、4和8的肽离子（鉴定为载脂蛋白血清转铁蛋白、补体成分C3 c和转铁蛋白）的总峰面积比（SPAR）值与非纤维化（S 0）至纤维化4期显著不同。由肽离子（蛋白质斑点1、4、8）建立的模型和由所有离子组合组成的模型的AUROC分别为0.848 ± 0.966（S2-S4 vs S 0-S1）和0.785 ± 0.875（S3-S4 vs S 0-S2）。只有转铁蛋白的肽离子模型有更好的灵敏度和特异性预测肝纤维化分期比天冬氨酸转氨酶血小板比率指数（APRI），FIB-4和Forn的index.ConclusionsSerum肽离子转铁蛋白，蛋白质组学MRM检测，是新的和有前途的生物标志物分期慢性乙型肝炎患者肝纤维化。
Background and aimBecause of the limitations of liver biopsy, reliable non-invasive serum biomarkers of liver fibrosis are needed. The aim of this study was to identify such markers by the use of serum proteomics in chronic hepatitis B (CHB).MethodsTwo-dimensional gel electrophoresis (2-DE) was used to identify differentially expressed protein spots in sera from 40 CHB patients [20 with mild fibrosis (S0–S1) and 20 with severe fibrosis (S3–S4)]. Mass spectrometry (MS) based multiple reaction monitoring (MRM) was used to quantify peptide ions of differential protein spots in another set of sera from 86 CHB patients with different liver fibrosis (S0–S4).ResultsSeven differentially expressed protein spots were found by 2-DE. Fourteen peptide ions of seven target protein spots were quantified by MS-based MRM. Summed peak areas ratio (SPAR) values of peptide ions from protein spot 1, 4 and 8, identified as apo serum transferrin, complement component C3c and transferrin, were significantly different from non-fibrosis (S0) to fibrosis stage 4. AUROCs of models established by peptide ions (protein spot 1, 4, 8) and model consisting of a combination of all ions were 0.848∼0.966 (S2–S4 versus S0–S1) and 0.785∼0.875 (S3–S4 versus S0–S2). Only the peptide ions model of transferrin had better sensitivity and specificity for predicting fibrosis stages than did aspartate aminotransferase-to-platelet ratio index (APRI), FIB-4 and Forn's index.ConclusionsSerum peptide ions of transferrin, detected by proteomic MRM, are new and promising biomarkers for staging liver fibrosis in CHB patients.
影响因子：
13.5
作者：
Sterling, Richard K.;Lissen, Eduardo;Nelson, Mark
通讯作者：
Nelson, Mark