Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI.

Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin, vitamin D binding protein and apolipoprotein AI.
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DOI:
10.1186/1423-0127-17-58
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发表时间:
2010-07-15
影响因子:
11
通讯作者:
Wang CC
Wang CC
中科院分区:
医学1区
文献类型:
--
作者:
Ho AS;Cheng CC;Lee SC;Liu ML;Lee JY;Wang WM;Wang CC

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评估肝纤维化的金标准是肝活检,这是有创的,并非没有风险。因此,寻找肝纤维化的无创性血清学标志物是一个重要的临床问题。共入组了16名健康志愿者和45名慢性丙型肝炎病毒(HCV)患者(F0:n = 16,F1:n = 7,F2:n = 17,F3:n = 8和F4:n = 13,根据METAVIR分类)。每个纤维化阶段的三个血清样品通过二维差异凝胶电泳(2D-DIGE)进行分析。采用MALDI-TOF/TOF和MASCOT技术对差异蛋白进行鉴定,并采用Western blotting和Bio-SpectrophotSuspension Array进行定量分析。确定了三个突出的候选生物标志物:α 2巨球蛋白(A2 M)上调;维生素D结合蛋白(VDBP)和载脂蛋白AI(ApoAI)下调。正常组、轻度组(F1/F2)和重度组(F3/F4)血清A2 M浓度差异有显著性(P < 0.01)。正常/轻度纤维化中VDBP和ApoAI的蛋白水平显著高于晚期纤维化中的蛋白水平(均p < 0.01)。这项研究不仅揭示了三个假定的肝纤维化生物标志物(A2 M,VDBP和ApoAI),而且还证明了这些标志物在不同阶段的纤维化中的差异表达。我们期望这些新的生物标志物的组合可以在临床上应用于预测肝纤维化的阶段,而不需要肝活检。
The gold standard of assessing liver fibrosis is liver biopsy, which is invasive and not without risk. Therefore, searching for noninvasive serologic biomarkers for liver fibrosis is an importantly clinical issue. A total of 16 healthy volunteers and 45 patients with chronic hepatitis C virus (HCV) were enrolled (F0: n = 16, F1: n = 7, F2: n = 17, F3: n = 8 and F4: n = 13, according to the METAVIR classification). Three serum samples of each fibrotic stage were analyzed by two-dimension difference gel electrophoresis (2D-DIGE). The differential proteins were identified by the cooperation of MALDI-TOF/TOF and MASCOT; then western blotting and Bio-Plex Suspension Array were used to quantify the protein levels. Three prominent candidate biomarkers were identified: alpha 2 macroglobulin (A2M) is up regulated; vitamin D binding protein (VDBP) and apolipoprotein AI (ApoAI) are down regulated. The serum concentration of A2M was significantly different among normal, mild (F1/F2) and advanced fibrosis (F3/F4) (p < 0.01). The protein levels of VDBP and ApoAI were significantly higher in normal/mild fibrosis, when compared to those in advanced fibrosis (both p < 0.01). This study not only reveals three putative biomarkers of liver fibrosis (A2M, VDBP and ApoAI) but also proves the differential expressions of those markers in different stages of fibrosis. We expect that combination of these novel biomarkers could be applied clinically to predict the stage of liver fibrosis without the need of liver biopsy.
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