Dataset Information

ESI-LC-MS Method for Haptoglobin Fucosylation Analysis in Hepatocellular Carcinoma and Liver Cirrhosis.

ABSTRACT: A method for the detection of fucosylated glycans from haptoglobin in patient serum has been developed that provides enhanced sensitivity. The workflow involves isolation of the haptoglobin using an HPLC-based affinity column followed by glycan removal, extraction, and desialylation. The fucosylated glycans are then derivatized by Meladrazine, which significantly enhances the detection of the glycans in electrospray ionization. The separation of the derivatized glycans in a HILIC column shows that eight glycans from haptoglobin can be detected using less than 1 ?L of a serum sample, with excellent reproducibility and quantitation, where without derivatization the glycans could not be detected. The ratio of the fucosylated peaks to their corresponding nonfucosylated forms shows that the fucosylated glycans are upregulated in the case of hepatocellular carcinoma (HCC) samples versus cirrhosis samples, where the relatively low abundance bifucosylated tetra-antennary form can be detected and may be a particularly good marker for HCC.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4670582 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Publications

ESI-LC-MS Method for Haptoglobin Fucosylation Analysis in Hepatocellular Carcinoma and Liver Cirrhosis.

Zhang Yiwei Y Zhu Jianhui J Yin Haidi H Marrero Jorge J Zhang Xin-Xiang XX Lubman David M DM

Journal of proteome research 20151103 12

A method for the detection of fucosylated glycans from haptoglobin in patient serum has been developed that provides enhanced sensitivity. The workflow involves isolation of the haptoglobin using an HPLC-based affinity column followed by glycan removal, extraction, and desialylation. The fucosylated glycans are then derivatized by Meladrazine, which significantly enhances the detection of the glycans in electrospray ionization. The separation of the derivatized glycans in a HILIC column shows th ...[more]

PMID: 26503433

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Project description:Chronic hepatitis B virus (CHB) infection is one of the primary risk factors associated with the development of hepatocellular carcinoma (HCC). Despite having been extensively studied, diagnosing early-stage HCC remains challenging, and diagnosed patients have a poor (3-5%) survival rate. Identifying new approaches to detect changes in the serum metabolic profiles of patients with CHB and liver cirrhosis (LC) may provide a valuable approach to better detect HCC at an early stage when it is still amenable to treatment, thereby improving patient prognosis and survival. In the present study, we, therefore, employed a liquid chromatography-mass spectrometry (LC-MS)-based approach to evaluate the serum metabolic profiles of 30 CHB patients, 29 LC patients, and 30 HCC patients. We then employed appropriate statistical methods to identify those metabolites that were best able to distinguish HCC cases from LC and CHB controls. A mass-based database was then used to putatively identify these metabolites. We then confirmed the identities of a subset of these metabolites through comparisons with the MS/MS fragmentation patterns and retention times of reference standards. The serum samples were then reanalyzed to quantify the levels of these selected metabolites and of other metabolites that have previously been identified as potential HCC biomarkers. Through this approach, we observed clear differences in the metabolite profiles of the CHB, LC, and HCC patient groups in both positive- and negative-ion modes. We found that the levels of taurodeoxy cholic acid (TCA) and 1,2-diacyl-3-β-d-galactosyl-sn-glycerol rose with the progression from CHB to LC to HCC, whereas levels of 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid were gradually reduced with liver disease progression in these groups. The ROC analysis showed that taurodeoxy cholic acid (TCA), 1,2-diacyl-3-β-d-galactosyl-sn-glycerol, 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid had a diagnosis performance with liver disease progression. These four metabolites have a significant correlation with alpha fetal protein (AFP) level and age. Our results highlight novel metabolic biomarkers that have the potential to be used for differentiating between CHB, LC, and HCC patients, thereby facilitating the identification and treatment of patients with early-stage HCC.

Dataset Information

ESI-LC-MS Method for Haptoglobin Fucosylation Analysis in Hepatocellular Carcinoma and Liver Cirrhosis.

Publications

ESI-LC-MS Method for Haptoglobin Fucosylation Analysis in Hepatocellular Carcinoma and Liver Cirrhosis.

Similar Datasets

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