Serum fibrinogen alpha C-chain 5.9 kDa fragment as a biomarker for early detection of hepatic fibrosis related to hepatitis C virus
Serum fibrinogen alpha C-chain 5.9 kDa fragment as a biomarker for early detection of hepatic fibrosis related to hepatitis C virus
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DOI：
10.1002/prca.201200094
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发表时间：
2013-06-01
影响因子：
2
通讯作者：
Nomura, Fumio
中科院分区：
文献类型：
--
作者：
Sogawa, Kazuyuki;Noda, Kenta;Nomura, Fumio
目的通过蛋白质组学分析发现的候选生物标志物的临床应用具有挑战性。本研究的目的是标准化的预分析条件，用于测量血清中纤维蛋白原α C链5.9 kDa片段（FIC 5.9）的水平，并测试该肽检测丙型肝炎病毒（HCV）相关慢性肝炎患者早期肝纤维化的诊断价值。实验设计通过夹心ELISA测量血清FIC 5.9水平。研究了温度、静脉穿刺和血清分离之间的时间以及所用收集管的类型对血清FIC 5.9水平的影响。然后评估血清FIC 5.9作为HCV所致肝纤维化的早期指标的诊断价值。结果FIC 5.9在静脉穿刺后产生，并具有时间和温度依赖性。89.5%的FI期患者FIC5.9值异常。受试者操作特征分析证实了FIC 5.9在早期检测纤维化方面优于其他常规标志物。结论：血清FIC 5.9水平可能是HCV相关慢性肝病肝纤维化的早期指标。这项研究提供了一个例子，从生物标志物的发现，蛋白质组分析，分析优化和初步的临床验证的管道。
Purpose Clinical application of biomarker candidates discovered by proteomic analysis is challenging. The purpose of this study was to standardize preanalytical conditions for measurement of serum levels of fibrinogen alpha C-chain 5.9 kDa fragment (FIC 5.9) and to test the diagnostic value of this peptide for detection of early hepatic fibrosis in patients with hepatitis C virus (HCV)-related chronic hepatitis. Experimental design Serum FIC 5.9 levels were measured by a sandwich ELISA. Effects on the serum FIC 5.9 level of temperature, the time between venipuncture and serum separation, and the types of collection tubes used were examined. The diagnostic value of serum FIC 5.9 as an early indicator of hepatic fibrosis due to HCV was then assessed. Results FIC 5.9 was produced in a time- and temperature-dependent manner after venipuncture. Abnormal FIC 5.9 values were found in 89.5% of FI stage patients. Receiver operating characteristic analyses confirmed the superiority of FIC 5.9 over other conventional markers for early detection of fibrosis. Conclusions and clinical relevance The serum FIC 5.9 level may be an early indicator of hepatic fibrosis in HCV-related chronic liver diseases. This study provides an example of a pipeline from biomarker discovery by proteome analysis to assay optimization and preliminary clinical validation.