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Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma

INTRODUCTION: Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosy...

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Autores principales: Pan, Huiying, Wu, Zhiyuan, Zhang, Haiping, Zhang, Jie, Liu, Yue, Li, Zhiwei, Feng, Wei, Wang, Guiqi, Liu, Yong, Zhao, Deli, Zhang, Zhiyi, Liu, Yuqin, Zhang, Zhe, Liu, Xiangtong, Tao, Lixin, Luo, Yanxia, Wang, Xiaonan, Yang, Xinghua, Zhang, Feng, Li, Xia, Guo, Xiuhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043232/
https://www.ncbi.nlm.nih.gov/pubmed/36999031
http://dx.doi.org/10.3389/fimmu.2023.981861
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author Pan, Huiying
Wu, Zhiyuan
Zhang, Haiping
Zhang, Jie
Liu, Yue
Li, Zhiwei
Feng, Wei
Wang, Guiqi
Liu, Yong
Zhao, Deli
Zhang, Zhiyi
Liu, Yuqin
Zhang, Zhe
Liu, Xiangtong
Tao, Lixin
Luo, Yanxia
Wang, Xiaonan
Yang, Xinghua
Zhang, Feng
Li, Xia
Guo, Xiuhua
author_facet Pan, Huiying
Wu, Zhiyuan
Zhang, Haiping
Zhang, Jie
Liu, Yue
Li, Zhiwei
Feng, Wei
Wang, Guiqi
Liu, Yong
Zhao, Deli
Zhang, Zhiyi
Liu, Yuqin
Zhang, Zhe
Liu, Xiangtong
Tao, Lixin
Luo, Yanxia
Wang, Xiaonan
Yang, Xinghua
Zhang, Feng
Li, Xia
Guo, Xiuhua
author_sort Pan, Huiying
collection PubMed
description INTRODUCTION: Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC. METHODS: In total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was composed by a stepwise ordinal logistic model in the discovery population. The receiver operating characteristic (ROC) curve with the bootstrapping procedure was used to assess the performance of the glycan score. RESULTS: In the discovery population, the adjusted OR of GP20 (digalactosylated monosialylated biantennary with core and antennary fucose), IGP33 (the ratio of all fucosylated monosyalilated and disialylated structures), IGP44 (the proportion of high mannose glycan structures in total neutral IgG glycans), IGP58 (the percentage of all fucosylated structures in total neutral IgG glycans), IGP75 (the incidence of bisecting GlcNAc in all fucosylated digalactosylated structures in total neutral IgG glycans), and the glycan score are 4.03 (95% CI: 3.03-5.36, P<0.001), 0.69 (95% CI: 0.55-0.87, P<0.001), 0.56 (95% CI: 0.45-0.69, P<0.001), 0.52 (95% CI: 0.41-0.65, P<0.001), 7.17 (95% CI: 4.77-10.79, P<0.001), and 2.86 (95% CI: 2.33-3.53, P<0.001), respectively. Individuals in the highest tertile of the glycan score own an increased risk (OR: 11.41), compared with those in the lowest. The average multi-class AUC are 0.822 (95% CI: 0.786-0.849). Findings are verified in the validation population, with an average AUC of 0.807 (95% CI: 0.758-0.864). DISCUSSION: Our study demonstrated that IgG N-glycans and the proposed glycan score appear to be promising predictive markers for ESCC, contributing to the early prevention of esophageal cancer. From the perspective of biological mechanism, IgG fucosylation and mannosylation might involve in the carcinogenesis progression of ESCC, and provide potential therapeutic targets for personalized interventions of cancer progression.
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spelling pubmed-100432322023-03-29 Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma Pan, Huiying Wu, Zhiyuan Zhang, Haiping Zhang, Jie Liu, Yue Li, Zhiwei Feng, Wei Wang, Guiqi Liu, Yong Zhao, Deli Zhang, Zhiyi Liu, Yuqin Zhang, Zhe Liu, Xiangtong Tao, Lixin Luo, Yanxia Wang, Xiaonan Yang, Xinghua Zhang, Feng Li, Xia Guo, Xiuhua Front Immunol Immunology INTRODUCTION: Altered Immunoglobulin G (IgG) N-glycosylation is associated with aging, inflammation, and diseases status, while its effect on esophageal squamous cell carcinoma (ESCC) remains unknown. As far as we know, this is the first study to explore and validate the association of IgG N-glycosylation and the carcinogenesis progression of ESCC, providing innovative biomarkers for the predictive identification and targeted prevention of ESCC. METHODS: In total, 496 individuals of ESCC (n=114), precancerosis (n=187) and controls (n=195) from the discovery population (n=348) and validation population (n=148) were recruited in the study. IgG N-glycosylation profile was analyzed and an ESCC-related glycan score was composed by a stepwise ordinal logistic model in the discovery population. The receiver operating characteristic (ROC) curve with the bootstrapping procedure was used to assess the performance of the glycan score. RESULTS: In the discovery population, the adjusted OR of GP20 (digalactosylated monosialylated biantennary with core and antennary fucose), IGP33 (the ratio of all fucosylated monosyalilated and disialylated structures), IGP44 (the proportion of high mannose glycan structures in total neutral IgG glycans), IGP58 (the percentage of all fucosylated structures in total neutral IgG glycans), IGP75 (the incidence of bisecting GlcNAc in all fucosylated digalactosylated structures in total neutral IgG glycans), and the glycan score are 4.03 (95% CI: 3.03-5.36, P<0.001), 0.69 (95% CI: 0.55-0.87, P<0.001), 0.56 (95% CI: 0.45-0.69, P<0.001), 0.52 (95% CI: 0.41-0.65, P<0.001), 7.17 (95% CI: 4.77-10.79, P<0.001), and 2.86 (95% CI: 2.33-3.53, P<0.001), respectively. Individuals in the highest tertile of the glycan score own an increased risk (OR: 11.41), compared with those in the lowest. The average multi-class AUC are 0.822 (95% CI: 0.786-0.849). Findings are verified in the validation population, with an average AUC of 0.807 (95% CI: 0.758-0.864). DISCUSSION: Our study demonstrated that IgG N-glycans and the proposed glycan score appear to be promising predictive markers for ESCC, contributing to the early prevention of esophageal cancer. From the perspective of biological mechanism, IgG fucosylation and mannosylation might involve in the carcinogenesis progression of ESCC, and provide potential therapeutic targets for personalized interventions of cancer progression. Frontiers Media S.A. 2023-03-14 /pmc/articles/PMC10043232/ /pubmed/36999031 http://dx.doi.org/10.3389/fimmu.2023.981861 Text en Copyright © 2023 Pan, Wu, Zhang, Zhang, Liu, Li, Feng, Wang, Liu, Zhao, Zhang, Liu, Zhang, Liu, Tao, Luo, Wang, Yang, Zhang, Li and Guo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Pan, Huiying
Wu, Zhiyuan
Zhang, Haiping
Zhang, Jie
Liu, Yue
Li, Zhiwei
Feng, Wei
Wang, Guiqi
Liu, Yong
Zhao, Deli
Zhang, Zhiyi
Liu, Yuqin
Zhang, Zhe
Liu, Xiangtong
Tao, Lixin
Luo, Yanxia
Wang, Xiaonan
Yang, Xinghua
Zhang, Feng
Li, Xia
Guo, Xiuhua
Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma
title Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma
title_full Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma
title_fullStr Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma
title_full_unstemmed Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma
title_short Identification and validation of IgG N-glycosylation biomarkers of esophageal carcinoma
title_sort identification and validation of igg n-glycosylation biomarkers of esophageal carcinoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043232/
https://www.ncbi.nlm.nih.gov/pubmed/36999031
http://dx.doi.org/10.3389/fimmu.2023.981861
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