N-linked glycoproteomic profiling in esophageal squamous cell carcinoma  

作　　者：Qi-Wei Liu Hao-Jie Ruan Wei-Xia Chao Meng-Xiang Li Ye-Lin Jiao Douglas G Ward She-Gan Gao Yi-Jun Qi 

机构地区：[1]Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment/Henan Key Laboratory of Cancer Epigenetics/Cancer Hospital,The First Affiliated Hospital,College of Clinical Medicine,Henan University of Science and Technology,Luoyang 471003,Henan Province,China [2]Department of Pathology,The First People’s Hospital of Luo Yang,Luoyang 471000,Henan Province,China [3]Institute of Cancer and Genomic Sciences,College of Medical and Dental Sciences,University of Birmingham,Birmingham B152TT,United Kingdom

出　　处：《World Journal of Gastroenterology》2022年第29期3869-3885,共17页世界胃肠病学杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China,No.81072039 and No.81872037.

摘　　要：BACKGROUND Mass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic sequencing.AIM To characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma(ESCC)via two complementary approaches.METHODS Using tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins,we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis(2-DE)-based and isobaric tags for relative and absolute quantification(iTRAQ)labeling-based mass spectrometry quantitation in parallel,followed by validation of candidate glycoprotein biomarkers by Western blot.RESULTS 2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins,respectively,with 15 in common,demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two approaches.Proteomaps showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with ESCC.Western blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D,and the downregulation of total haptoglobin,high-mannose clusterin,and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC tissues.The serum levels of glycosylated fractions of clusterin,prolinearginine-rich end leucine-rich repeat protein,and haptoglobin in patients with ESCC were remarkably higher than those in healthy controls.CONCLUSION Our study provides insights into the aberrant N-linked glycoproteome associated with ESCC,which will be a valuable resource for future investigations.

关 键 词：Esophageal squamous cell carcinoma N-linked glycoprotein Post-translational modification LECTIN Cathepsin D HAPTOGLOBIN 14-3-3ζ 

分 类 号：R735.1[医药卫生—肿瘤]