High-throughput site-specific N-glycoproteomics reveals glyco-signatures for liver disease diagnosis  

作　　者：Zhenyu Sun Bin Fu Guoli Wang Lei Zhang Ruofan Xu Ying Zhang Haojie Lu 

机构地区：[1]Shanghai Cancer Center and Institutes of Biomedical Sciences,Fudan University,Shanghai 200032,China [2]Department of Chemistry and NHC Key Laboratory of Glycoconjugates Research,Fudan University,Shanghai 200032,China [3]Eleanor Roosevelt College,University of California San Diego,La Jolla,CA 92093,USA

出　　处：《National Science Review》2023年第1期209-220,共12页国家科学评论（英文版）

基　　金：the National Key Research and Development Program of China(2020YFE0202200);the National Natural Science Foundation of China(22174021,21974025and 82121004);the project of Shanghai Key Laboratory of Kidney and Blood Purification;Shanghai Pujiang Program(2019PJD003);the Innovative Research Team of High-Level Local University in Shanghai。

摘　　要：The glycoproteome has emerged as a prominent target for screening biomarkers,as altered glycosylation is a hallmark of cancer cells.In this work,we incorporated tandem mass tag labeling into quantitative glycoproteomics by developing a chemical labeling-assisted complementary dissociation method for the multiplexed analysis of intact N-glycopeptides.Benefiting from the complementary nature of two different mass spectrometry dissociation methods for identification and multiplex labeling for quantification of intact N-glycopeptides,we conducted the most comprehensive site-specific and subclass-specific N-glycosylation profiling of human serum immunoglobulin G(IgG)to date.By analysing the serum of 90 human patients with varying severities of liver diseases,as well as healthy controls,we identified that the combination of IgG1-H3N5F1 and IgG4-H4N3 can be used for distinguishing between different stages of liver diseases.Finally,we used targeted parallel reaction monitoring to successfully validate the expression changes of glycosylation in liver diseases in a different sample cohort that included 45 serum samples.

关 键 词：GLYCOPROTEOMICS HIGH-THROUGHPUT quantification N-glycopeptides liver disease 

分 类 号：R575[医药卫生—消化系统]