High-throughput intact Glycopeptide quantification strategy with targeted-MS (HTiGQs-target) reveals site-specific IgG N-glycopeptides as biomarkers for hepatic disorder diagnosis and staging

Xuejiao Liu; Bin Fu; Jierong Chen; Zhenyu Sun; Dongdong Zheng; Zhonghua Li; Bing Gu; Ying Zhang; Haojie Lu

doi:10.1016/j.carbpol.2023.121499

High-throughput intact Glycopeptide quantification strategy with targeted-MS (HTiGQs-target) reveals site-specific IgG N-glycopeptides as biomarkers for hepatic disorder diagnosis and staging

Carbohydr Polym. 2024 Feb 1:325:121499. doi: 10.1016/j.carbpol.2023.121499. Epub 2023 Oct 16.

Authors

Xuejiao Liu¹, Bin Fu², Jierong Chen³, Zhenyu Sun⁴, Dongdong Zheng⁵, Zhonghua Li⁶, Bing Gu⁷, Ying Zhang⁸, Haojie Lu⁹

Affiliations

¹ Liver Cancer Institute of Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Chemistry and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai 200032, China.
² Department of Chemistry and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai 200032, China.
³ Laboratory Medicine of Guangdong Provincial People's Hospital and Guangdong, Academy of Medical Sciences, Guangzhou, Guangdong 510000, China.
⁴ Liver Cancer Institute of Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
⁵ Department of Ultrasound, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
⁶ Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
⁷ Laboratory Medicine of Guangdong Provincial People's Hospital and Guangdong, Academy of Medical Sciences, Guangzhou, Guangdong 510000, China. Electronic address: gb20031129@163.com.
⁸ Liver Cancer Institute of Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Chemistry and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai 200032, China. Electronic address: ying@fudan.edu.cn.
⁹ Liver Cancer Institute of Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Chemistry and NHC Key Laboratory of Glycoconjugates Research, Fudan University, Shanghai 200032, China. Electronic address: luhaojie@fudan.edu.cn.

PMID: 38008487
DOI: 10.1016/j.carbpol.2023.121499

Abstract

Liver disease is one of the leading causes of global mortality, and identifying biomarkers for diagnosing the progression of liver diseases is crucial for improving its outcomes. Targeted mass spectrometry technology is a powerful tool with unique advantages for verifying biomarker candidates and clinical applications. It is particularly useful in validating protein biomarkers with post-translational modifications, eliminating the need for site-specific antibodies. Especially, targeted mass spectrometry technique is particularly critical for translation of glycoproteins into clinical applications as there are no site-specific antibodies for N-glycosylation. Nevertheless, its limitation in analyzing only one sample per run has become apparent when dealing with a large number of clinical samples. Herein, we developed a high-throughput intact N-glycopeptides quantification strategy with targeted-MS (HTiGQs-Target), which allows the validation of 20 samples per run with an average analysis time of only 3 min per sample. We applied HTiGQs-Target in a cohort of 461 serum samples (including 120 healthy controls (HC), 127 chronic hepatitis B (CHB) cases, 106 liver cirrhosis (LC) cases, and 108 hepatocellular carcinomas (HCC) cases) and found that a panel of 10 IgG N-glycopeptides have strong clinical utility in evaluating the severity of the liver disease.

Keywords: Biomarker; High-throughput; IgG N-Glycopeptides; Liver disease; Parallel reaction monitoring.

MeSH terms

Biomarkers, Tumor
Carcinoma, Hepatocellular* / diagnosis
Glycopeptides
Humans
Immunoglobulin G
Liver Neoplasms* / diagnosis

Substances

Glycopeptides
Biomarkers, Tumor
Immunoglobulin G