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血清纤维化标志物:BIPED 分类与新表位方法相结合,开发新型生物标志物。

Serum markers of liver fibrosis: combining the BIPED classification and the neo-epitope approach in the development of new biomarkers.

机构信息

Department of Pharmacology, Nordic Bioscience, Herlev, Denmark.

出版信息

Dis Markers. 2010;28(1):15-28. doi: 10.3233/DMA-2010-0678.

Abstract

BACKGROUND

Fibrosis is a central histological feature of chronic liver diseases and is characterized by the accumulation and reorganization of the extracellular matrix. The gold standard for assessment of fibrosis is histological evaluation of a percutaneous liver biopsy. Albeit a considerable effort have been invested in finding alternative non-invasive approaches, these have not been sufficiently successful to replace biopsy assessment.

AIM

To identify the extracellular matrix proteins of interest, that as protein degradation fragments produced during extracellular matrix metabolism neo-epitopes, may be targeted for novel biochemical marker development in fibrosis. We used the recently proposed BIPED system (Burden of disease, Investigative, Prognostic, Efficacy and Diagnostic) to characterise present serological markers.

METHODS

Pubmed was search for keywords; Liver fibrosis, neo-epitopes, biomarkers, clinical trail, extra cellular matrix, protease, degradation, fragment.

RESULTS AND CONCLUSION

Implementation of BIPED categorization in the development and validation of fibrosis biomarkers to simplify and standardize the use of existing and future biomarkers seems advantageous. In addition, a systematic use of the neo-epitope approach, i.e. the quantification of peptide epitopes generated from enzymatic cleavage of proteins during extracellular remodeling, may prove productive in the quest to find new markers of liver fibrosis.

摘要

背景

纤维化是慢性肝病的中心组织学特征,其特征是细胞外基质的积累和重排。纤维化评估的金标准是经皮肝活检的组织学评估。尽管已经投入了相当大的努力来寻找替代的非侵入性方法,但这些方法还没有成功到足以替代活检评估。

目的

鉴定细胞外基质蛋白,这些蛋白作为细胞外基质代谢过程中产生的蛋白降解片段,可能成为纤维化新生化标志物开发的新靶点。我们使用了最近提出的 BIPED 系统(疾病负担、调查、预后、疗效和诊断)来描述目前的血清标志物。

方法

在 Pubmed 上搜索关键词:肝纤维化、新表位、生物标志物、临床试验、细胞外基质、蛋白酶、降解、片段。

结果和结论

在纤维化生物标志物的开发和验证中实施 BIPED 分类,以简化和标准化现有和未来生物标志物的使用似乎是有利的。此外,系统地使用新表位方法,即定量分析在细胞外重塑过程中酶切产生的蛋白质肽表位,可能有助于寻找新的肝纤维化标志物。

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