PRM-MS Quantitative Analysis of Isomeric N -Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma

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 performed a comprehensive...

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Published in:Metabolites 2021-08, Vol.11 (8), p.563
Main Authors: Gutierrez Reyes, Cristian D, Huang, Yifan, Atashi, Mojgan, Zhang, Jie, Zhu, Jianhui, Liu, Suyu, Parikh, Neehar D, Singal, Amit G, Dai, Jianliang, Lubman, David M, Mechref, Yehia
Format: Article
Language:English
Subjects:
Antibiotics
Cirrhosis
Glycopeptides
Glycosylation
Haptoglobin
Hepatocellular carcinoma
hepatocellular carcinoma (HCC)
Liquid chromatography
Liver cancer
Liver cirrhosis
Mass spectroscopy
N-glycopeptides
Patients
Peptides
PRM
Quantitative analysis
Retention
Ultrasonic imaging
α-Fetoprotein
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Summary: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 performed a comprehensive liquid chromatography-parallel reaction monitoring-mass spectrometry (LC-PRM-MS) approach, where a targeted parallel reaction monitoring (PRM) strategy was coupled 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 -glycopeptides, mainly located in the Hp glycosylation site Asn207. Four -glycopeptides were found to have significant changes in abundance between cirrhosis and HCC samples ( < 0.05). Strategic combinations of the significant -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 -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 -glycopeptide Asn207 + 5-6-0-1 better estimated AUC with respect to AFP (AUC = 0.81, and AUC + 5-6-0-1 = 0.88, respectively).
ISSN:2218-1989
2218-1989
DOI:10.3390/metabo11080563