Quantification of Intact O-Glycopeptides on Haptoglobin in Sera of Patients With Hepatocellular Carcinoma and Liver Cirrhosis

Hong Shu; Hong Shu; Lei Zhang; Yiwei Chen; Yijie Guo; Limin Li; Fanghua Chen; Zhao Cao; Guoquan Yan; Chunlai Lu; Chao Liu; Shu Zhang

doi:10.3389/fchem.2021.705341

Frontiers in Chemistry (Jul 2021)

Quantification of Intact O-Glycopeptides on Haptoglobin in Sera of Patients With Hepatocellular Carcinoma and Liver Cirrhosis

Hong Shu,
Hong Shu,
Lei Zhang,
Yiwei Chen,
Yijie Guo,
Limin Li,
Fanghua Chen,
Zhao Cao,
Guoquan Yan,
Chunlai Lu,
Chao Liu,
Shu Zhang

Affiliations

Hong Shu: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
Hong Shu: Department of Clinical Laboratory, Cancer Hospital of Guangxi Medical University, Nanning, China
Lei Zhang: Institutes of Biomedical Sciences, Fudan University, Shanghai, China
Yiwei Chen: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
Yijie Guo: Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, China
Limin Li: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China
Fanghua Chen: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China
Zhao Cao: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China
Guoquan Yan: Institutes of Biomedical Sciences, Fudan University, Shanghai, China
Chunlai Lu: Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
Chao Liu: Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University, Beijing, China
Shu Zhang: Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China

DOI: https://doi.org/10.3389/fchem.2021.705341
Journal volume & issue: Vol. 9

Abstract

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Haptoglobin (Hp) is one of the acute-phase response proteins secreted by the liver, and its aberrant N-glycosylation was previously reported in hepatocellular carcinoma (HCC). Limited studies on Hp O-glycosylation have been previously reported. In this study, we aimed to discover and confirm its O-glycosylation in HCC based on lectin binding and mass spectrometry (MS) detection. First, serum Hp was purified from patients with liver cirrhosis (LC) and HCC, respectively. Then, five lectins with Gal or GalNAc monosaccharide specificity were chosen to perform lectin blot, and the results showed that Hp in HCC bound to these lectins in a much stronger manner than that in LC. Furthermore, label-free quantification based on MS was performed. A total of 26 intact O-glycopeptides were identified on Hp, and most of them were elevated in HCC as compared to LC. Among them, the intensity of HYEGS316TVPEK (H1N1S1) on Hp was the highest in HCC patients. Increased HYEGS316TVPEK (H1N1S1) in HCC was quantified and confirmed using the MS method based on 18O/16O C-terminal labeling and multiple reaction monitoring. This study provided a comprehensive understanding of the glycosylation of Hp in liver diseases.

Published in Frontiers in Chemistry

ISSN: 2296-2646 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Chemistry
Website: http://journal.frontiersin.org/journal/chemistry

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