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Structures of disease-specific serum alpha-fetoprotein isoforms (2000)_香港中文大学化學病理學系 (CPY)研究成果

香港中文大学 辅仁网/2017-06-20

Structures of disease-specific serum alpha-fetoprotein isoforms
Publication in refereed journal


香港中文大学研究人员 ( 现职)
何宗信教授 (化学病理学系)
潘全威教授 (儿科学系)
庄立信教授 (肿瘤学系)


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Web of Sciencehttp://aims.cuhk.edu.hk/converis/portal/Publication/43WOS source URL

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摘要Alpha-fetoprotein (AFP) is widely used as a serological marker in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT). By application of isoelectric focusing (IEF) disease-specific AFP isoforms can be identified Three major bands are apparent: + I (associated with 'benign' liver disease), + II (associated with HCC) and +[I( (associated with NSGCT). Recently we have characterized the predominant glycans of human serum AFP and now report the application of these findings and electrospray ionization-mass spectrometry (ESI-MS) to the determination of the glycan composition of the isoforms present in the sera of 12 patients with MCC and of one patient with NSGCT. ESI-MS allowed simultaneous identification of various AFP glycoforms in purified serum AFP. Seven glycoforms were identified, but with different abundance in the sera of the HCC patients, whereas six glycoforms were identified in the serum from the NSGCT patient. The glycan structures of these glycoforms were deduced from their observed masses. AFP glycoforms carrying a single biantennary complex-type N-glycan appeared as the predominant glycoforms, whereas those carrying both N-glycan and O-glycan appeared as minor glycoforms. Correlation between the abundance of the AFP glycoforms and the IEF band intensity suggested that different degrees in sialylation cause the formation of isoforms. This contention was subsequently supported by the ESI-MS and kinetic in vitro desialylation studies on purified Bands + I and + II AFPs. Our findings indicate that HCC-associated isoforms (Band + [I) represent a group of glycoproteins whose carbohydrate structures are ail characterized by being mono-sialylated, whereas those associated with benign liver disease and NSGCT are di- and a-sialo species, respectively. Knowledge of the structure of the tumour-specific isoforms should form an important basis for clinically useful assays. (C) 2000 Cancer Research Campaign.

着者Johnson PJ, Poon TCW, Hjelm NM, Ho CS, Blake C, Ho SKW
期刊名称British Journal of Cancer
出版年份2000
月份11
日期1
卷号83
期次10
出版社CHURCHILL LIVINGSTONE
页次1330 - 1337
国际标準期刊号0007-0920
电子国际标準期刊号1532-1827
语言英式英语

关键词alpha-fetoprotein isoform; glycosylation; hepatocellular carcinoma; non-seminomatous germ cell tumours; protein structure
Web of Science 学科类别Oncology; ONCOLOGY

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