N-linked glycan changes of serum haptoglobin β chain in liver disease patients

Zhang, Shu; Shu, Hong; Luo, Kaixuan; Kang, Xiaonan; Zhang, Ying; Lu, Haojie; Liu, Yinkun

doi:10.1039/c1mb05020f

Cited by 49 publications

(53 citation statements)

References 31 publications

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“…Altered glycosylation of plasma proteins is a common finding associated with liver diseases, including cirrhosis, cancer and hepatitis [26,[28][29][30][31][32][33][34]. An increase in branching and fucosylation of transferrin N-glycans has previously been reported in patients with hepatocellular carcinoma [26,32,34], which was similar to the pattern found in the samples with di-tri bridging.…”

Section: Discussionsupporting

confidence: 53%

Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety

Landberg

Åström

Kågedal

et al. 2012

Clinica Chimica Acta

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Methods: Nineteen serum samples showing di-tri bridging when analyzed by HPLC were collected. Transferrin was purified by affinity chromatography, and N-linked oligosaccharides were released enzymatically. The N-glycans were further analyzed by high performance anion-exchange chromatography with pulsed amperometric detection and MALDI-TOF mass spectrometry. Results:The HPLC-analysis showed three different types of glycoform patterns. The Nglycans from fifteen samples showed patterns with increased number of triantennary structures containing one or two fucose residues. One sample contained an increased amount of triantennary glycans without fucose. Three samples showed a glycosylation pattern similar to normal transferrin. Conclusions:The di-tri bridging phenomenon was associated with alterations in transferrin glycosylation in the majority of cases. Transferrin contained a higher extent of triantennary and often fucosylated N-linked oligosaccharides. These results may be important in future diagnostic approaches to liver diseases.3

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Section: Discussionsupporting

confidence: 53%

Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety

Landberg

Åström

Kågedal

et al. 2012

Clinica Chimica Acta

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“…In the case of HCT116 cells, cancer cells themselves cannot produce Fuc-Hpt, indicating that their surrounding normal cells such as hepatocytes and lymphocytes produced Fuc-Hpt. After we reported that Fuc-Hpt is a promising biomarker for pancreatic cancer, many researchers have reported increases in Fuc-Hpt in sera of patients with different cancers such as colon cancer [24], liver cancer [25], lung cancer [26], and pancreatic cancer [27]. …”

Section: Fucosylated Haptoglobinmentioning

confidence: 99%

Fucosylation Is a Promising Target for Cancer Diagnosis and Therapy

et al. 2012

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Oligosaccharides, sequences of carbohydrates conjugated to proteins and lipids, are arguably the most abundant and structurally diverse class of molecules. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. Recent advances in glycomics have identified several types of glyco-biomarkers containing fucosylation that are linked to certain types of cancer. Fucosylated alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma because it is more specific than alpha-fetoprotein. High levels of fucosylated haptoglobin have also been found in sera of patients with various carcinomas. We have recently established a simple lectin-antibody ELISA to measure fucosylated haptoglobin and to investigate its clinical use. Cellular fucosylation is dependent upon fucosyltransferase activity and the level of its donor substrate, guanosine diphosphate (GDP)-fucose. GDP-mannose-4,6-dehydratase (GMDS) is a key enzyme involved in the synthesis of GDP-fucose. Mutations of GMDS found in colon cancer cells induced a malignant phenotype, leading to rapid growth in athymic mice resistant to natural killer cells. This review describes the role of fucosylated haptoglobin as a cancer biomarker, and discusses the possible biological role of fucosylation in cancer development.

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“…10,11 Haptoglobin is one of the acute phase proteins (APP) secreted by the liver, which binds to hemoglobin and plays an important role in response to inflammation and malignancy. 12 It consists of β, α-1, and α-2 chains, with four potential N -glycosylation sites on its β chain.…”

Section: Introductionmentioning

confidence: 99%

“…10,11,18 A MALDI-QIT-TOF analysis of N -glycans of serum Hp revealed that a biantennary fucosylated glycan was highly increased in patients with cirrhosis and HCC compared to healthy controls. 11 Recently, a quantitative liquid chromatography–mass spectrometry multiple reaction monitoring analysis of site-specific glycoforms of Hp showed that multiply fucosylated glycoforms increased significantly in the liver disease group compared to that in healthy controls. 18 However, in these studies, mass spectrometric analyses of haptoglobin glycans were performed using either pooled sera or a limited number of cases of liver diseases.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Serum Haptoglobin Fucosylation in Hepatocellular Carcinoma and Liver Cirrhosis of Different Etiologies

et al. 2014

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We have developed herein a quantitative mass spectrometry-based approach to analyze the etiology-related alterations in fucosylation degree of serum haptoglobin in patients with liver cirrhosis and hepatocellular carcinoma (HCC). The three most common etiologies, including infection with hepatitis B virus (HBV), infection with hepatitis C virus (HCV), and heavy alcohol consumption (ALC), were investigated. Only 10 μL of serum was used in this assay in which haptoglobin was immunoprecipitated using a monoclonal antibody. The N-glycans of haptoglobin were released with PNGase F, desialylated, and permethylated prior to MALDI-QIT-TOF MS analysis. In total, N-glycan profiles derived from 104 individual patient samples were quantified (14 healthy controls, 40 cirrhosis, and 50 HCCs). A unique pattern of bifucosylated tetra-antennary glycan, with both core and antennary fucosylation, was identified in HCC patients. Quantitative analysis indicated that the increased fucosylation degree was highly associated with HBV- and ALC-related HCC patients compared to that of the corresponding cirrhosis patients. Notably, the bifucosylation degree was distinctly increased in HCC patients versus that in cirrhosis of all etiologies. The elevated bifucosylation degree of haptoglobin can discriminate early stage HCC patients from cirrhosis in each etiologic category, which may be used to provide a potential marker for early detection and to predict HCC in patients with cirrhosis.

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N-linked glycan changes of serum haptoglobin β chain in liver disease patients

Cited by 49 publications

References 31 publications

Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety

Disialo–trisialo bridging of transferrin is due to increased branching and fucosylation of the carbohydrate moiety

Fucosylation Is a Promising Target for Cancer Diagnosis and Therapy

Analysis of Serum Haptoglobin Fucosylation in Hepatocellular Carcinoma and Liver Cirrhosis of Different Etiologies

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