The Thomsen-Friedenreich Antigen-Specific Antibody Signatures in Patients with Breast Cancer

Abstract

Alterations in the glycosylation of serum total immunoglobulins show these antibodies to have a diagnostic potential for cancer but the disease-related Abs to the tumor-associated antigens, including glycans, have still poorly been investigated in this respect. We analysed serum samples from patients with breast carcinoma (n = 196) and controls (n = 64) for the level of Thomsen-Friedenreich (TF) antigen-specific antibody isotypes, their sialylation, interrelationships, and the avidity by using ELISA with the synthetic TF-polyacrylamide conjugate as an antigen and the sialic acid-specific Sambucus nigra agglutinin (SNA) and ammonium thiocyanate as a chaotrope. An increased sialylation of IgG and IgM, but a lower SNA reactivity of IgA TF antibodies, and a higher level and avidity of the TF-specific IgA were found in cancer patients. Other cancer-related signatures were the highly significant increase of the IgG/IgA ratio and the very low SNA/IgA index in cancer, including patients with an early stage of the disease. These changes showed a good diagnostic potential with about 80% accuracy. Thus, the level of naturally occurring anti-TF antigen antibodies, their sialylation profile, isotype distribution, and avidity displayed cancer-specific changes that could serve as novel noninvasive Ab-based biomarkers for early breast cancer.

Figure 1

The level of TF-specific IgG, IgM, and IgA antibodies in controls and breast cancer patients. Each dot represents one individual and the group median is indicated by horizontal lines. P values were calculated by the Mann–Whitney U test and are shown for significant differences.

Figure 2

Different anti-TF antibody isotype ratios in cancer patients and controls. P values are shown for significant differences.

Figure 3

The binding of SNA lectin to TF-specific antibodies in the serum samples of cancer patients and controls. The group median is indicated by horizontal lines. P values are shown for significant differences.

Figure 4

The anti-TF IgG, IgM, and IgA SNA indexes in patients and controls. P values are shown for significant differences.

Figure 5

The avidity of anti-TF IgG, IgM, and IgA antibodies in controls and cancer patients.

Figure 6

The correlation between the SNA lectin binding and the avidity of anti-TF IgG, IgM, and IgA in breast cancer patients.

Figure 7

A receiver operator characteristic (ROC) curve analysis for anti-TF IgA-related parameters// SNA/IgA index and the avidity of IgA. (a) SNA/IgA index for all cancer patients; (b) SNA/IgA index for patients with 0-1 stage of cancer: (c) IgA avidity index for all breast cancer patients. The area under the ROC curve represents the diagnostic accuracy of changes in cancer.