Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection.

Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection.
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DOI:
10.1186/1479-5876-5-33
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发表时间:
2007-07-11
影响因子:
7.4
通讯作者:
McHutchison JG
McHutchison JG
中科院分区:
医学2区
文献类型:
--
作者:
White IR;Patel K;Symonds WT;Dev A;Griffin P;Tsokanas N;Skehel M;Liu C;Zekry A;Cutler P;Gattu M;Rockey DC;Berrey MM;McHutchison JG

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尽管肝活检广泛用于评估纤维化,但它有几个重要的缺点,包括它是半定量的,侵入性的,并受到采样和观察者变异性的限制。非侵入性血清生物标志物可能更准确地反映纤维化过程。为了确定纤维化的潜在生物标志物,我们比较了慢性丙型肝炎(CHC)病毒感染和纤维化患者的血清蛋白表达谱。从1600例CHC患者的家系数据库中回顾性确定了21例无或轻度纤维化患者(METAVIR分期F0,F1)和23例晚期纤维化患者(F3,F4)。所有样本都经过仔细的表型分析,并根据年龄、性别、种族、体重指数、基因型、感染持续时间、饮酒和病毒载量进行匹配。使用2D聚丙烯酰胺凝胶电泳/LC-MS/MS平台以盲法进行表达谱分析。采用偏最小二乘判别分析和似然比统计对两组间蛋白质表达的个体差异进行排序。在晚期纤维化患者中,7个蛋白质点被鉴定为显著升高(α2-巨球蛋白、触珠蛋白、白蛋白)或降低(补体C-4、血清视黄醇结合蛋白、载脂蛋白A-1和载脂蛋白A-IV的两种亚型)。现有的非侵入性血清标志物组包括三种单独的蛋白质,触珠蛋白、载脂蛋白A-1和α2-巨球蛋白。通过表达谱鉴定的生物标志物可能有助于开发更准确的标志物算法,以更好地定量肝纤维化和监测疾病进展。
Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis. Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups. Seven individual protein spots were identified as either significantly increased (α2-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α2-macroglobulin, are included in existing non-invasive serum marker panels. Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.
DOI: 10.1186/1476-5926-3-8
发表时间: 2004-09-23
期刊: Comparative hepatology
影响因子: --
作者:
Poynard T;Imbert-Bismut F;Munteanu M;Messous D;Myers RP;Thabut D;Ratziu V;Mercadier A;Benhamou Y;Hainque B
通讯作者: Hainque B
DOI: 10.1002/hep.20506
发表时间: 2005-01-01
期刊: HEPATOLOGY
影响因子: 13.5
作者:
Ziol, M;Handra-Luca, A;Beaugrand, M
通讯作者: Beaugrand, M
DOI: 10.1016/j.exphem.2004.06.006
发表时间: 2004-09-01
影响因子: 2.6
作者:
Kwak, JY;Ma, TZ;Kwak, YG
通讯作者: Kwak, YG
DOI: 10.1074/mcp.m200037-mcp200
发表时间: 2002-06-01
影响因子: 7
作者:
Ostrowski, LE;Blackburn, K;Boucher, RC
通讯作者: Boucher, RC
DOI: 10.1002/hep.21046
发表时间: 2006-02-01
期刊: HEPATOLOGY
影响因子: 13.5
作者:
Rockey, DC;Bissell, DM
通讯作者: Bissell, DM