Relationship Between N-linked Oligosaccharide Chains of Human Serum Immunoglobulin G and Serum Tumor Markers with Non-small Cell Lung Cancer Progression

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: Fr1 (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.