State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, 102206, China.
Sci China Life Sci. 2011 May;54(5):393-402. doi: 10.1007/s11427-011-4165-y. Epub 2011 May 15.
A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease, treatment decisions, and assessing drug efficacy. This study evaluated plasma proteomic profiling via an N-terminal isotope tagging strategy coupled with liquid chromatography/Fourier transform ion cyclotron resonance mass spectrometry measurement to detect liver fibrosis staging. Pooled plasma from different liver fibrosis stages, which were assessed in advance by the current gold-standard of liver biopsy, was quantitatively analyzed. A total of 72 plasma proteins were found to be dysregulated during the fibrogenesis process, and this finding constituted a valuable candidate plasma biomarker bank for follow-up analysis. Validation results of fibronectin by Western blotting reconfirmed the mass-based data. Ingenuity Pathways Analysis showed four types of metabolic networks for the functional effect of liver fibrosis disease in chronic hepatitis B patients. Consequently, quantitative proteomics via the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers for liver fibrosis. We quantitatively monitored the fibrogenesis process in CHB patients. We discovered many new valuable candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis disease. These results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement of clinical diagnosis and treatment.
一种非侵入性的诊断方法对于评估肝脏疾病的严重程度、治疗决策以及评估药物疗效至关重要。本研究通过 N 端同位素标记策略与液相色谱/傅里叶变换离子回旋共振质谱联用的方法评估蛋白质组谱，以检测肝纤维化分期。通过当前肝活检的金标准预先评估不同肝纤维化阶段的混合血浆，并对其进行定量分析。在纤维化过程中发现了 72 种失调的血浆蛋白，这一发现构成了后续分析有价值的候选血浆生物标志物库。Western blot 对纤维连接蛋白的验证结果进一步证实了基于质谱的数据。通路分析显示，慢性乙型肝炎患者肝纤维化疾病的功能效应涉及四种代谢网络。因此，通过 N 端乙酰化同位素标记技术的定量蛋白质组学为筛选肝纤维化的候选血浆生物标志物提供了一种有效且有用的工具。我们对 CHB 患者的纤维化过程进行了定量监测。我们发现了许多新的有价值的候选肝纤维化诊断生物标志物，并且部分鉴定了肝纤维化疾病涉及的机制。这些结果提供了对肝纤维化病理生理学的更清晰理解，也有望改善临床诊断和治疗。
