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Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: A glycoproteomic approach
Ang I.L.1; Poon T.C.W.1; Lai P.B.S.1; Chan A.T.C.1; Ngai S.-M.1; Hui A.Y.1; Johnson P.J.2; Sung J.J.Y.1
2006-10-01
Source PublicationJournal of Proteome Research
ISSN15353893
Volume5Issue:10Pages:2691-2700
Abstract

Increased serum haptoglobin concentration and changes in its glycosylation have been reported in certain cancer types. Information for hepatocellular carcinoma (HCC) has not yet been available. In this study, we aimed to carry out a systematic analysis of serum concentrations of haptoglobin (Hp) and its glycoforms in the patients with HCC and noncancer patients only with chronic liver diseases (CLD) and to examine their clinical values. This study was divided into two major parts, (1) measurement of serum Hp concentration, and investigation of its value in the diagnosis of HCC, and (2) quantitative analysis of Hp glycoforms with alpha-2,6-sialylation and/or alpha-1,6- fucosylation by using lectin affinity purification and 2D gel electrophoresis and investigation of their relationships with tumor stage. The concentrations of serum Hp in HCC patients were significantly higher than those in noncancer patients with CLD. With the use of serum concentrations of Hp and alpha-fetoprotein, a logistic regression (LR) model was developed from the training data set and used to classify the validation cases. At a specificity of 95%, the sensitivity for HCC detection was 79%. Comparing serum concentrations of alpha-2,6-sialylated Hp (S-Hp) and alpha-1,6-fucosylated Hp (F-Hp) between HCC and CLD patients suggests that purification of S-Hp and F-Hp could enrich the glycosylation variants associated with HCC. 2D gel analysis of S-Hp and F-Hp identified a total of 18 glycoforms. A unique pattern of Hp glycoforms comprising both hypersialylated fucosylated and hyposialylated fucosylated species was found in the HCC patients. Serum concentrations of these glycoproteins were significantly higher in the patients with advanced tumors, suggesting their tumor-specific nature. We have shown that serum Hp is a potential biomarker in the diagnosis of HCC. The combined use of Hp and AFP could greatly improve the diagnostic accuracy. A unique pattern of Hp glycoforms with altered sialylation and fucosylation is specific to HCC and associated tumor progression. © 2006 American Chemical Society.

KeywordHaptoglobin Glycoform Sialylation Fucosylation Glycosylation Hepatocellular Carcinoma Diagnosis
DOI10.1021/pr060109r
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemical Research Methods
WOS IDWOS:000241053100021
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Cited Times [WOS]:113   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorPoon T.C.W.
Affiliation1.Prince of Wales Hospital Hong Kong
2.University of Birmingham
Recommended Citation
GB/T 7714
Ang I.L.,Poon T.C.W.,Lai P.B.S.,et al. Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: A glycoproteomic approach[J]. Journal of Proteome Research,2006,5(10):2691-2700.
APA Ang I.L..,Poon T.C.W..,Lai P.B.S..,Chan A.T.C..,Ngai S.-M..,...&Sung J.J.Y..(2006).Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: A glycoproteomic approach.Journal of Proteome Research,5(10),2691-2700.
MLA Ang I.L.,et al."Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: A glycoproteomic approach".Journal of Proteome Research 5.10(2006):2691-2700.
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