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


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.


CONCLUSIONS
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.
Kanoh
Yuhsaku
Y
Department of Laboratory Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Ohara
Tadashi
T
Mashiko
Takaomi
T
Abe
Tadashi
T
Masuda
Noriyuki
N
Akahoshi
Tohru
T
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D008175:Lung Neoplasms / Q000097:blood / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000378:metabolism*
D014408:Biomarkers, Tumor; D007074:Immunoglobulin G; D009844:Oligosaccharides