Prm-ms quantitative analysis of isomeric n-glycopeptides derived from human serum haptoglobin of patients with cirrhosis and hepatocellular carcinoma

Cristian D. Gutierrez Reyes, Yifan Huang, Mojgan Atashi, Jie Zhang, Jianhui Zhu, Suyu Liu, Neehar D. Parikh, Amit G. Singal, Jianliang Dai, David M. Lubman, Yehia Mechref

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Currently, surveillance strategies have inadequate performance for cirrhosis and early detection of hepatocellular carcinoma (HCC). The glycosylation of serum haptoglobin has shown to have significant differences between cirrhosis and HCC, thus can be used for diagnosis. We per-formed a comprehensive liquid chromatography—parallel reaction monitoring—mass spectrome-try (LC-PRM-MS) approach, where a targeted parallel reaction monitoring (PRM) strategy was cou-pled to a powerful LC system, to study the site-specific isomerism of haptoglobin (Hp) extracted from cirrhosis and HCC patients. We found that our strategy was able to identify a large number of isomeric N-glycopeptides, mainly located in the Hp glycosylation site Asn207. Four N-glycopep-tides were found to have significant changes in abundance between cirrhosis and HCC samples (p < 0.05). Strategic combinations of the significant N-glycopeptides, either with alpha-fetoprotein (AFP) or themselves, better estimate the areas under the curve (AUC) of their respective receiver operating characteristic (ROC) curves with respect to AFP. The combination of AFP with the isomeric sialylated fucosylated N-glycopeptides Asn207 + 5-6-1-2 and Asn207 + 5-6-1-3, resulted with an AUC value of 0.98, while the AUC value for AFP alone was 0.85. When comparing cirrhosis vs. early HCC, the isomeric N-glycopeptide Asn207 + 5-6-0-1 better estimated AUC with respect to AFP (AUCAFP = 0.81, and AUCAsn207 + 5-6-0-1 = 0.88, respectively).

Original languageEnglish (US)
Article number563
JournalMetabolites
Volume11
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

  • Cirrhosis
  • Haptoglobin
  • Hepatocellular carcinoma (HCC)
  • N-glycopeptides
  • PRM

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology

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