PRM-MS Quantitative Analysis of Isomeric <i>N</i>-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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doaj-1a88444d53054e619fedfa1abb02bb332021-08-26T14:03:58ZengMDPI AGMetabolites2218-19892021-08-011156356310.3390/metabo11080563PRM-MS Quantitative Analysis of Isomeric <i>N</i>-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular CarcinomaCristian D. Gutierrez Reyes0Yifan Huang1Mojgan Atashi2Jie Zhang3Jianhui Zhu4Suyu Liu5Neehar D. Parikh6Amit G. Singal7Jianliang Dai8David M. Lubman9Yehia Mechref10Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USADepartment of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USADepartment of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USADepartment of Surgery, The University of Michigan, Ann Arbor, MI 48109, USADepartment of Surgery, The University of Michigan, Ann Arbor, MI 48109, USADepartment of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADivision of Gastroenterology and Hepatology, The University of Michigan, Ann Arbor, MI 48109, USADivision of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Surgery, The University of Michigan, Ann Arbor, MI 48109, USADepartment of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USACurrently, 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 <i>N</i>-glycopeptides, mainly located in the Hp glycosylation site Asn207. Four <i>N</i>-glycopeptides were found to have significant changes in abundance between cirrhosis and HCC samples (<i>p</i> < 0.05). Strategic combinations of the significant <i>N</i>-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 <i>N</i>-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 <i>N</i>-glycopeptide Asn207 + 5-6-0-1 better estimated AUC with respect to AFP (AUC<sub>AFP</sub> = 0.81, and AUC<sub>Asn207</sub> + 5-6-0-1 = 0.88, respectively).https://www.mdpi.com/2218-1989/11/8/563PRM<i>N</i>-glycopeptideshaptoglobincirrhosishepatocellular carcinoma (HCC) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 PRM-MS Quantitative Analysis of Isomeric <i>N</i>-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma Metabolites PRM <i>N</i>-glycopeptides haptoglobin cirrhosis hepatocellular carcinoma (HCC) |
author_facet |
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 |
author_sort |
Cristian D. Gutierrez Reyes |
title |
PRM-MS Quantitative Analysis of Isomeric <i>N</i>-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma |
title_short |
PRM-MS Quantitative Analysis of Isomeric <i>N</i>-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma |
title_full |
PRM-MS Quantitative Analysis of Isomeric <i>N</i>-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma |
title_fullStr |
PRM-MS Quantitative Analysis of Isomeric <i>N</i>-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma |
title_full_unstemmed |
PRM-MS Quantitative Analysis of Isomeric <i>N</i>-Glycopeptides Derived from Human Serum Haptoglobin of Patients with Cirrhosis and Hepatocellular Carcinoma |
title_sort |
prm-ms quantitative analysis of isomeric <i>n</i>-glycopeptides derived from human serum haptoglobin of patients with cirrhosis and hepatocellular carcinoma |
publisher |
MDPI AG |
series |
Metabolites |
issn |
2218-1989 |
publishDate |
2021-08-01 |
description |
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 <i>N</i>-glycopeptides, mainly located in the Hp glycosylation site Asn207. Four <i>N</i>-glycopeptides were found to have significant changes in abundance between cirrhosis and HCC samples (<i>p</i> < 0.05). Strategic combinations of the significant <i>N</i>-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 <i>N</i>-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 <i>N</i>-glycopeptide Asn207 + 5-6-0-1 better estimated AUC with respect to AFP (AUC<sub>AFP</sub> = 0.81, and AUC<sub>Asn207</sub> + 5-6-0-1 = 0.88, respectively). |
topic |
PRM <i>N</i>-glycopeptides haptoglobin cirrhosis hepatocellular carcinoma (HCC) |
url |
https://www.mdpi.com/2218-1989/11/8/563 |
work_keys_str_mv |
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