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Open Access 01-12-2022 | Metastasis | Research

An N-glycoproteomic site-mapping analysis reveals glycoprotein alterations in esophageal squamous cell carcinoma

Authors: Yingzhen Gao, Liuyi Shen, Tianyue Dong, Xin Yang, Heyang Cui, Yanlin Guo, Yanchun Ma, Pengzhou Kong, Xiaolong Cheng, Ling Zhang, Yongping Cui

Published in: Journal of Translational Medicine | Issue 1/2022

Abstract

Background

Aberrant glycosylation has been recognized as a hallmark of cancer and N-glycosylation is one of the main types of glycosylation in eukaryotes. Although N-glycoproteomics has made contributions to the discovery of biomarkers in a variety of cancers, less is known about the abnormal glycosylation signatures in esophageal squamous cell carcinoma (ESCC).

Methods

In this study, we reported the proteomics and N-glycoproteomic site-mapping analysis of eight pairs of ESCC tissues and adjacent normal tissues. With zic-HILIC enrichment, TMT-based isobaric labeling, LC–MS/MS analysis, differentially expressed N-glycosylation was quantitatively characterized. Lectin affinity enrichment combined with western blot was used to validate the potential biomarkers in ESCC.

Results

A series of differentially expressed glycoproteins (e.g., LAMP2, PLOD2) and enriched signaling pathways (e.g., metabolism-related pathway, ECM-receptor interaction, focal adhesion) were identified. Besides that, seven significantly enriched motifs were found from the identified N-glycosylation sites. Three clusters were identified after conducting the dynamic profiling analysis of glycoprotein change during lymph node metastasis progression. Further validation found that the elevated fucosylation level of ITGB1, CD276 contributed to the occurrence and development of ESCC, which might be the potential biomarkers in ESCC.

Conclusion

In summary, we characterized the N-glycosylation and N-glycoprotein alterations associated with ESCC. The typical changes in glycoprotein expression and glycosylation occupancy identified in our study will not only be used as ESCC biomarkers but also improve the understanding of ESCC biology.

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Title: An N-glycoproteomic site-mapping analysis reveals glycoprotein alterations in esophageal squamous cell carcinoma
Authors: Yingzhen Gao
Liuyi Shen
Tianyue Dong
Xin Yang
Heyang Cui
Yanlin Guo
Yanchun Ma
Pengzhou Kong
Xiaolong Cheng
Ling Zhang
Yongping Cui
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Metastasis
Published in: Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-022-03489-2

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