Increased Avidity of the Sambucus nigra Lectin-Reactive Antibodies to the Thomsen-Friedenreich Antigen as a Potential Biomarker for Gastric Cancer.

Oleg Kurtenkov,Kersti Klaamas

doi:10.1155/2015/761908

Oleg Kurtenkov, Kersti Klaamas

Open Access

https://doi.org/10.1155/2015/761908

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Journal: Disease markers	Publication Date: Jan 1, 2015
Citations: 37	License type: CC BY 3.0

Affiliation: National Institute for Health Development

Abstract

Aim. To determine whether the naturally occurring Thomsen-Friedenreich (TF) antigen-specific antibodies differ in avidity between cancer patients and controls to find a novel biomarker for stomach cancer. Methods. Serum samples were taken from patients with cancer and controls. The level of TF-specific antibodies and their sialylation were determined using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specific Sambucus nigra agglutinin (SNA). The avidity was determined using ammonium thiocyanate as a chaotrope. Results. A significantly higher SNA lectin binding to anti-TF antibodies was found in cancer patients irrespective of disease stage. The avidity of only IgM TF-specific antibodies was significantly higher in cancer patients compared to controls. The SNA-positive anti-TF antibodies of cancer patients showed a significantly higher avidity, P < 0.001. The sensitivity and specificity of this increase for gastric cancer were 73.53% and 73.08%, respectively, with a 73.2% diagnostic accuracy. The higher avidity of SNA-reactive anti-TF antibodies was associated with a benefit in survival of stage 3 cancer patients. Conclusion. The SNA-reactive TF-specific antibodies display a significantly higher avidity in gastric cancer patients compared to controls, which can be used as a potential serologic biomarker for gastric cancer. It appears that IgM is the main target responsible for the above changes.

Highlights

Over the past two decades protein posttranslational modifications have attracted ever-increasing attention in medical research
The Sambucus nigra agglutinin (SNA)-reactive TF-specific antibodies display a significantly higher avidity in gastric cancer patients compared to controls, which can be used as a potential serologic biomarker for gastric cancer
In the present study we show, for the first time, that gastric cancer is associated with a significantly higher avidity (P < 0.001) of Sambucus nigra Agglutinin- (SNA-)positive TF-specific antibodies that may be used as a serologic biomarker for gastric cancer

Summary

Introduction

Over the past two decades protein posttranslational modifications have attracted ever-increasing attention in medical research. The altered immature O-glycophenotype often observed in cancer cells leads to the expression of modified glycopeptide epitopes and tumor-associated glycans (TAGs) that may be autoimmunogenic and recognized by autoantibodies [1,2,3,4,5,6,7,8,9]. TAGs are considered as a promising target for cancer immunotherapy [20,21,22,23]. The overexpression of these commonly hidden glycotopes and the reduced level of naturally occurring antiTF or anti-Tn antibodies are associated with tumor progression and aggressiveness and a patients survival rate [16, 24,25,26,27,28,29]. The TF antigen seems to play a crucial role in the adhesion of cancer cells to the endothelium through the interaction with galectin-3, thereby promoting metastases [30, 31]

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Conclusion