Plasma biomarker screening for liver fibrosis with the N-terminal isotope tagging strategy  

作　　者：LI ShuLong LIU Xin WEI Lai WANG HuiFen ZHANG JiYang WEI HanDong QIAN XiaoHong JIANG Ying HE FuChu 

机构地区：[1]State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China [2]Beijing Institute of Biotechnology, Beijing 100071, China [3]People 's Hospital of Peking University, Beijing 100044, China [4]302 Military Hospital of China, Beijing 100039, China [5]Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China [6]Central Laboratory, Yantai Yu-Huang-Ding Hospital, Yantai 264000, China

出　　处：《Science China(Life Sciences)》2011年第5期393-402,共10页中国科学（生命科学英文版）

基　　金：supported by the National Basic Research Program of China(Grant Nos.2011CB910601,2011CB910700,2010CB912700 and 2011CB505304);the National High Technology Research and Development Program of China (Grant No.2006AA02A308);National Natural Science Foundation of China(Grant Nos.30700356,30700988,30972909,81000192,81001470 and 81010064);Chinese State Key Project Specialized for Infectious Diseases (Grant Nos.2008ZX10002-016 and 2009ZX10004-103);the National Key Technologies R&D Program for New Drugs (Grant No.2009ZX09301-002);the International Scientific Collaboration Program (Grant Nos.2009DFB33070 and 2010DFA31260);State Key Laboratory of Proteomics(Grant Nos.SKLP-Y200901 and SKLP-O200901)

摘　　要：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.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.

关 键 词：quantitative proteomics fiver fibrosis BIOMARKER PLASMA hepatitis B virus 

分 类 号：S828.45[农业科学—畜牧学] P618.130.1[农业科学—畜牧兽医]