Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour.
Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour.
复制标题
DOI：
10.1038/sj.bjc.6690828
复制
发表时间：
1999-12
影响因子：
8.8
通讯作者：
Townsend RR
中科院分区：
文献类型：
--
作者：
Johnson PJ;Poon TC;Hjelm NM;Ho CS;Ho SK;Welby C;Stevenson D;Patel T;Parekh R;Townsend RR
虽然血清甲胎蛋白（AFP）的估计被广泛用于肝细胞癌（HCC）和非腺瘤性生殖细胞肿瘤（NSGCT）的诊断，但该试验的临床实用性受到特异性低的限制。然而，存在AFP的糖型，其可能对特定肿瘤更具特异性。以前，由于人血清中AFP水平低，无法进行详细分析。我们在这里报告的应用荧光标记，顺序外切糖苷酶消化，高效液相色谱和基质辅助激光解吸电离飞行时间质谱，以确定从肝癌和NSGCT患者的纯化血清AFP的聚糖结构。发现了11个主要聚糖，其中7个是N-连接的，4个是O-连接的，与蛋白质骨架。N-连接聚糖的结构（均为双触角复合型，具有不同程度的唾液酸化、岩藻糖基化和半乳糖基化）与先前报告的结构一致。O-连接聚糖（三种具有不同唾液酸化程度的粘蛋白O-GalNAc型聚糖，一种O-HexNAc单糖聚糖）之前尚未报道。粘蛋白O-GalNAc型聚糖的发现得到了通过分子建模分析AFP结构预测蛋白骨架上潜在O-GalNAc糖基化位点的支持。有了这些结构的知识，就有可能开发出更特异的检测HCC和NSGCT的方法。© 1999癌症研究运动© 1999癌症研究运动
Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N-linked, and four were O-linked, to the protein backbone. The structure of the N-linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O-linked glycans (three mucin O-GalNAc type glycans with variable degrees of sialylation, one O-HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O-GalNAc type glycans was supported by the prediction of potential O-GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT. © 1999 Cancer Research Campaign © 1999 Cancer Research Campaign
登录
查看更多内容
影响因子：
29.4
作者：
SHEU, JC;SUNG, JL;LEE, CZ
通讯作者：
LEE, CZ
影响因子：
2.3
作者：
FERRANTI, P;PUCCI, P;MALORNI, A
通讯作者：
MALORNI, A
影响因子：
5
作者：
Shimizu, K;Katoh, H;Matsuura, S
通讯作者：
Matsuura, S
影响因子：
4.6
作者：
KAY, PH;WELLS, FC;GOLDSTRAW, P
通讯作者：
GOLDSTRAW, P
影响因子：
6.2
作者：
JOHNSON, PJ;HO, S;YUEN, J
通讯作者：
YUEN, J