人血清免疫球蛋白G的N-连接寡糖链与非小细胞肺癌进展相关血清肿瘤标志物之间的关系

Relationship between N-linked oligosaccharide chains of human serum immunoglobulin G and serum tumor markers with non-small cell lung cancer progression.

作者信息

Kanoh Yuhsaku, Ohara Tadashi, Mashiko Takaomi, Abe Tadashi, Masuda Noriyuki, Akahoshi Tohru

机构信息

Department of Laboratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.

出版信息

Anticancer Res. 2006 Nov-Dec;26(6B):4293-7.

PMID:17201147

Abstract

BACKGROUND

It has been demonstrated that increased expression of the sialyl Le(x) sugar chains on cancer cells influences cellular adhesion to vascular-endothelial cells. Therefore, it was thought that alterations in the sugar chain structure of E-cadherin, a calcium dependent adhesion molecule, influence the metastasis of cancer cells.

MATERIALS AND METHODS

In this study, N-linked oligosaccharides of human serum immunoglobulin G (IgG) were analyzed in 12 patients with non-small cell lung cancer (NSCLC) (6 localized cancer: 3 adenocarcinomas and 3 squamous cell carcinomas; 6 metastatic cancer: 3 adenocarcinomas and 3 squamous cell carcinomas) and 10 healthy controls using fluorophore-associated carbohydrate electrophoresis (FACE). The relationship between changes in sugar chain structure and serum concentrations of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) were evaluated. CEA levels in the sera were determined using an enzyme immunoassay, and CYFRA21-1 levels were determined using an enzyme chemiluminescent immunoassay.

RESULTS

Fri (monogalactosyl IgG oligosaccharides) and Fr2 (digalactosyl IgG oligosaccharides) decreased, while Fr4 (agalactosyl IgG oligosaccharides) significantly increased (p < 0.01-0.05) with NSCLC progression. The Fr4/Fr1+Fr2 ratio increased with NSCLC progression, and the ratios in localized and metastatic NSCLC were significantly higher than in healthy controls (p < 0.01 and p < 0.01, respectively). There was a strong correlation between serum CEA levels and Fr4 (r = 0.91) and a significant correlation between serum CEA levels and the Fr4/Fr1+Fr2 ratio (r = 0.83, p < 0.05) in patients with lung adenocarcinoma. There was a significant correlation between serum CYFRA21-1 levels and Fr4 (r = 0.88, p < 0.001) and a positive correlation between serum CYFRA21-1 levels and the Fr4/Fr1+Fr2 ratio (r = 0.38) in patients with lung squamous cell carcinoma.

CONCLUSION

The analysis of serum IgG N-linked oligosaccharide chain structures by FACE may be an auxiliary indicator of serum tumor markers for monitoring NSCLC progression.

摘要

背景

已证实癌细胞上唾液酸化Le(x)糖链表达增加会影响细胞与血管内皮细胞的黏附。因此，人们认为钙依赖性黏附分子E-钙黏蛋白糖链结构的改变会影响癌细胞的转移。

材料与方法

在本研究中，使用荧光团相关碳水化合物电泳（FACE）分析了12例非小细胞肺癌（NSCLC）患者（6例局限性癌：3例腺癌和3例鳞状细胞癌；6例转移性癌：3例腺癌和3例鳞状细胞癌）和10名健康对照者血清免疫球蛋白G（IgG）的N-连接寡糖。评估了糖链结构变化与癌胚抗原（CEA）和细胞角蛋白19片段（CYFRA21-1）血清浓度之间的关系。血清CEA水平采用酶免疫法测定，CYFRA21-1水平采用酶化学发光免疫法测定。