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α1-酸性糖蛋白岩藻糖基化作为癌症进展和预后的标志物

alpha1-acid glycoprotein fucosylation as a marker of carcinoma progression and prognosis.

作者信息

Hashimoto Shinji, Asao Takayuki, Takahashi Junko, Yagihashi Yuko, Nishimura Toyo, Saniabadi Abby R, Poland Dennis C W, van Dijk Willem, Kuwano Hiroyuki, Kochibe Naohisa, Yazawa Shin

机构信息

Department of General Surgical Science (Surgery 1), Gunma University, Graduate School of Medicine, Maebashi, Japan.

出版信息

Cancer. 2004 Dec 15;101(12):2825-36. doi: 10.1002/cncr.20713.

Abstract

BACKGROUND

Serum alpha1-acid glycoprotein (AGP), an acute-phase protein secreted by the liver, carries alpha(1,3)-fucosylated structures on its 5 highly branched, N-linked sugar chains.

METHODS

Serum AGP levels in patients with various types of malignancies (n=214 patients) were measured using an enzyme-linked immunosorbent assay with anti-AGP antibody. To investigate glycoforms that differed in their degree of branching and extent of fucosylation, serum AGP samples were analyzed by crossed affinoimmunoelectrophoresis (CAIE) with concanavalin A, and Aleuria aurantia lectin (AAL), and anti-AGP antibody.

RESULTS

A significant difference (P <0.001) in serum AGP levels was observed in preoperative patients compared with levels in the healthy control group, but the levels in individual patients did not reflect their clinical status. Conversely, it was found not only that the patterns of AGP glycoforms differed widely in the patient group compared with the healthy control group, but they also changed depending on each patient's clinical status. Furthermore, AGP glycoforms seemed to be appropriate markers of disease progression and prognosis according to follow-up studies of 45 patients during prolonged preoperative and postoperative periods.

CONCLUSIONS

Patients with advanced malignancies who had AGP glycoforms that contained highly fucosylated triantennary and tetraantennary sugar chains for long periods after surgery were likely to have a poor prognosis. However, patients who had AGP glycoforms without such changes were expected to have a good prognosis.

摘要

背景

血清α1-酸性糖蛋白(AGP)是一种由肝脏分泌的急性期蛋白,其5条高度分支的N-连接糖链上带有α(1,3)-岩藻糖基化结构。

方法

使用抗AGP抗体的酶联免疫吸附测定法测量各类恶性肿瘤患者(n = 214例患者)的血清AGP水平。为了研究分支程度和岩藻糖基化程度不同的糖型,血清AGP样本通过与伴刀豆球蛋白A、橙黄银耳凝集素(AAL)和抗AGP抗体进行交叉亲和免疫电泳(CAIE)分析。

结果

与健康对照组相比,术前患者的血清AGP水平存在显著差异(P <0.001),但个体患者的水平并未反映其临床状态。相反,发现不仅患者组中AGP糖型的模式与健康对照组相比差异很大,而且它们还根据每个患者的临床状态而变化。此外,根据对45例患者在术前和术后较长时期的随访研究,AGP糖型似乎是疾病进展和预后的合适标志物。

结论

术后长期具有包含高度岩藻糖基化三天线和四天线糖链的AGP糖型的晚期恶性肿瘤患者预后可能较差。然而,AGP糖型没有此类变化的患者预计预后良好。

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