Liu QW, Ruan HJ, Chao WX, Li MX, Jiao YL, Ward DG, Gao SG, Qi YJ. N-linked glycoproteomic profiling in esophageal squamous cell carcinoma. World J Gastroenterol 2022; 28(29): 3869-3885 [PMID: 36157541 DOI: 10.3748/wjg.v28.i29.3869]
Corresponding Author of This Article
Yi-Jun Qi, MD, PhD, Professor, 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, No. 29 Jinghua Road, Luoyang 471003, Henan Province, China. qiyijun@haust.edu.cn
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Aug 7, 2022; 28(29): 3869-3885 Published online Aug 7, 2022. doi: 10.3748/wjg.v28.i29.3869
N-linked glycoproteomic profiling in esophageal squamous cell carcinoma
Qi-Wei Liu, Hao-Jie Ruan, Wei-Xia Chao, Meng-Xiang Li, Ye-Lin Jiao, Douglas G Ward, She-Gan Gao, Yi-Jun Qi
Qi-Wei Liu, Hao-Jie Ruan, Wei-Xia Chao, Meng-Xiang Li, She-Gan Gao, Yi-Jun Qi, 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
Ye-Lin Jiao, Department of Pathology, The First People’s Hospital of Luo Yang, Luoyang 471000, Henan Province, China
Douglas G Ward, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom
Author contributions: Qi YJ and Gao SG designed and coordinated the study; Liu QW, Ruan HJ, Chao WX, Li MX, Jiao YL, and Ward DG performed the experiments, and acquired and analyzed the data; Qi YJ and Ward DG wrote the manuscript; and all authors approved the final version of the article.
Supported byNational Natural Science Foundation of China, No. 81072039 and No. 81872037.
Institutional review board statement: The study was approved by the Ethics Committee of the Medical School, Henan University, China (ethics ref: 108) and conducted in accordance with the ethical guidelines of the 1975 Declaration of Helsinki.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yi-Jun Qi, MD, PhD, Professor, 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, No. 29 Jinghua Road, Luoyang 471003, Henan Province, China. qiyijun@haust.edu.cn
Received: January 14, 2022 Peer-review started: January 14, 2022 First decision: April 12, 2022 Revised: April 26, 2022 Accepted: July 6, 2022 Article in press: July 6, 2022 Published online: August 7, 2022 Processing time: 200 Days and 16.2 Hours
Abstract
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 down-regulation 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, proline-arginine-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.
Core Tip: The N-linked glycoproteome was comprehensively profiled by two-dimensional gel electrophoresis-based and isobaric tags for relative and absolute quantification (iTRAQ) labeling-based mass spectrometry quantitation in parallel after N-linked glycoprotein enrichment by a tandem of multilectin affinity chromatography. The iTRAQ labeling-based quantitative proteomic profiling outperformed protein spot intensity quantification used by two-dimensional gel electrophoresis. A total of 411 N-linked glycoproteins were identified, including 128 up-regulated and 283 down-regulated glycoproteins with differential expression, which provide the scientific community with a dataset of glycoproteins associated with esophageal squamous cell carcinoma for in-depth investigation.
