High-Throughput Profiling of Serological Immunoglobulin G N-Glycome as a Noninvasive Biomarker of Gastrointestinal Cancers

被引：6

作者：

Liu, Pengcheng ^{[1
]}

Wang, Xiaobing ^{[2
]}

Dun, Aishe ^{[3
]}

Li, Yutong ^{[2
]}

Li, Houqiang ^{[1
]}

Wang, Lu ^{[1
]}

Zhang, Yichun ^{[1
]}

Li, Cancan ^{[4
]}

Zhang, Jinxia ^{[4
]}

Zhang, Xiaoyu ^{[5
]}

Ma, Lixing ^{[6
]}

Hou, Haifeng ^{[6
,7
]}

机构：

[1] Shandong First Med Univ & Shandong Acad Med Sci, Sch Publ Hlth, Jinan 250117, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Natl Clin Res Ctr Canc, State Key Lab Mol Oncol,Canc Hosp, Beijing 100021, Peoples R China

[3] Shandong First Med Univ & Shandong Acad Med Sci, Sch Stomatol, Jinan 250117, Peoples R China

[4] Capital Med Univ, Sch Publ Hlth, Beijing Key Lab Clin Epidemiol, Beijing 100069, Peoples R China

[5] Capital Med Univ, Beijing Sanbo Brain Hosp, Beijing 100093, Peoples R China

[6] Shandong First Med Univ, Dept Gastroenterol, Affiliated Hosp 2, Tai An 271000, Peoples R China

[7] Shandong First Med Univ & Shandong Acad Med Sci, Sch Publ Hlth, Dept Epidemiol, Jinan 250117, Peoples R China

来源：

ENGINEERING | 2023年 / 26卷

基金：

中国国家自然科学基金;

关键词：

Gastrointestinal cancer; Glycosylation; Immunoglobulin G; Diagnostic biomarker; Gastrointestinal (GI) cancers; ANTIINFLAMMATORY ACTIVITY; IGG GALACTOSYLATION; TUMOR PROGRESSION; GLYCOSYLATION; FC; INFLAMMATION; ASSOCIATION; PERFORMANCE; MECHANISMS; DIAGNOSIS;

D O I：

10.1016/j.eng.2023.02.008

中图分类号：

T [工业技术];

学科分类号：

08 ;

摘要：

Immunoglobulin G (IgG) N-glycosylation plays a crucial role in the development of inflammatory diseases. This study aimed to evaluate the diagnostic performance of IgG for gastrointestinal (GI) cancer subtypes. A total of 749 GI cancer patients were enrolled from the Cancer Hospital, Chinese Academy of Medical Sciences, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC) patients. Hydrophilic interaction liquid chromatography using ultra-performance liquid chromatography (HILIC-UPLC) was employed to analyze the composition of the plasma IgG Nglycome. The levels of circulating inflammatory cytokines were detected by means of a Bio-Plex Pro Human Th17 Cytokine Assay. Canonical correlation analysis (CCA) was used to explore the correlation between IgG N-glycosylation patterns and inflammatory cytokines. A Lasso algorithm, accompanied by a logistic regression model, was used to develop a glycan-based model for differentiating GI cancer patients from healthy individuals. The levels of sialylation and galactosylation were significantly decreased among EC, GC, CRC, and PC patients, whereas the abundance of glycans with bisecting Nacetylglucosamine (GlcNAc) was increased in GI cancer patients in comparison with the healthy controls. Moreover, only PC patients had a decreased level of fucosylation. The levels of interleukin 1b (IL-1b), IL31, and soluble CD40 ligand (sCD40L) were significantly higher in GI cancer patients than in the controls. In addition, the composition of IgG N-glycans was correlated with that of inflammatory cytokines (r = 0.556). The glycan-based models for diagnosing GI cancers exhibited an excellent performance, with areas under the receiver operating characteristic curves (AUCs) of 0.972 for EC, 0.871 for GC, 0.867 for CRC, and 0.907 for PC. Our findings demonstrate that IgG N-glycosylation plays an important role in modulating the pathogenesis of GI cancers. Serological IgG N-glycosylation is thus a potential candidate for noninvasively assisting in the clinical diagnosis of GI cancer subtypes.(c) 2023 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：44 / 53

页数：10