The IgG Fc glycans strongly influence the Fcγ receptor interactions and Fc-mediated effector mechanisms. Changes in the structure of IgG glycans are associated with various diseases, such as infections and autoimmunity. However, the possible role of Fc glycans in tumor immunity is not yet fully understood. The aim of this study was to profile the Fc N-glycans of IgG samples from patients with gastric cancer (n = 80) and controls (n = 51) using LC-ESI-MS method to correlate the findings with stage of cancer and patients survival. Analysis of 32 different IgG N-glycans revealed significant increase of agalactosylated (GnGnF, GnGn(bi)F), and decrease of galactosylated (AGn(bi), AGn(bi)F, AA(bi), AAF) and monosialylated IgG glycoforms (NaAF, NaA(bi)) in cancer patients. A statistically significant increase of Fc fucosylation was observed in tumor stage II and III whereas reverse changes were found for the presence of bisecting GlcNAc. Higher level of fully sialylated glycans and elevated expression of glycans with bisecting GlcNAc were associated with better survival rate. Our findings provide the first evidence that the changes in Fc glycan profile may predict the survival of patients with gastric cancer. Cancer stage-dependent changes in Fc fucosylation and the bisecting N-acteylglucosamine expression as well as an association of several IgG glycoforms with the survival suggest that IgG glycosylation is related to pathogenesis of cancer and progression of the disease.

Humoral immune responses to the MUC1 peptide and to MUC1-related Thomsen-Friedenreich (TF) glycotope was investigated in patients with gastric cancer (n = 247), chronic gastroduodenal diseases (n = 199) and in healthy blood donors (n = 100). Data were correlated with disease type, stage of cancer, tumor morphology and survival. MUC1 IgG antibody levels were higher in patients with gastric cancer (p < 0.0001) than in healthy controls. Higher levels of anti-MUC1 IgG were also detected in patients with ulcer of the stomach (p = 0.015) and in atrophic gastritis (p = 0.027). Compared to blood donors, significantly lower levels of anti-TF IgG were found both in the cancer (p = 0.002) and in the benign group (p < 0.0001). At early stages of cancer a positive correlation (p < 0.0001) was found between MUC1 IgG and TF IgG antibody levels. High levels of TF IgG antibodies were significantly associated with a benefit in survival of gastric cancer patients (p = 0.003). A similar though weaker association was observed for patients with high levels of MUC1 IgG antibodies and locoregional disease (stage I-III) (p = 0.037). Thus IgG immune responses to MUC1 are increased in patients with gastric cancer. High levels of either TF IgG or MUC1 IgG antibodies may predict better outcome in surgically treated patients with gastric cancer.

Helicobocter pylori infection is considered to be a risk factor for gastric cancer. A high prevalence of H. pylori infection and high gastric-cancer incidence are characteristic of the Estonian population. To evaluate the relationship between these 2 events, we studied the seroprevalence of H. pylori in gastric cancer patients (n = 182) and in healthy blood donors (n = 306).A relative anti-H. pylori IgG antibody activity, as detected by ELSA and immunoblot patterns, was correlated with age, stage of the disease arid tumor morphology. A significantly higher H. pylori seroprevalence was found in patients in the early stages of tumor development compared with both advanced cancer patients and controls. No significant difference in H. pylori seroprevalence between patients with the intestinal and diffuse types of tumor growth was observed. A decline in the recognition of putatively cross-reacting (33-66 kDa) antigens was noted in the cancer group. The response to vacuolating toxinrelated 85-kDa and CagA 120-kDa protein antigens was not altered and was observed more often in the younger group of cancer patients.

A possible association of serum anti-T IgM and IgG antibody levels with Lewis blood-group phenotype was investigated in 168 blood donors and 132 gastric cancer patients using ELISA with synthetic T-disaccharide-polyacrylamide conjugate as antigen. The donors of Le(a-b+) phenotype showed the highest anti-T IgM level irrespective of ABO(H) blood group. A significant decrease in anti-T IgM in serum was observed among cancer patients of Le(a-b+) phenotype: 95% of weak responders versus 17.5% for related groups of donors (p < 10(-6)). In contrast, no significant difference between patients and donors was found for Le(b-) individuals. Thus, a level of natural anti-T antibodies in serum of blood donors and its decrease in patients with gastric cancer are related to Le(a,b) phenotype. This should be taken into account where anti-T antibody level in the serum is used as a tumour marker or for monitoring patients during cancer immunotherapy with mucin-type vaccines.

Objective: To evaluate the relation of the level of serum anti-TF, -Tn and -αGal carbohydrate antibodies to survival in gastrointestinal cancer patients.Methods: The level of anti-TF (Thomsen-Friedenreich antigen), -Tn and -αGal IgG was analysed in the serum of patients with gastric (n = 83) and colorectal (n = 51) cancers in the long-term follow-up, using ELISA with polyacrylamide glycoconjugates. To evaluate overall survival and the risk of death, the Kaplan-Meier method and the Cox proportional hazards model were used in the univariate analysis of patients groups.Results: A significantly better survival was observed: (1) in patients with an increased level of anti-TF antibodies (all, stage III, T2-4, N1-2 and G3; P = 0.004-0.038, HR = 0.16-0.46); and (2) in patients with an increased level of anti-Tn antibodies (G1-2 tumors; P = 0.034-0.042, HR = 0.34-0.47). A significantly worse survival was observed in gastrointestinal, gastric and colorectal groups with an increased level of serum anti-αGal antibodies. This association depended on the patho-morphology of tumors (all, stages I-II, III, T2-4, N0, N1-2 and G1-2; P = 0.006-0.048, HR = 1.99-2.33). In the combined assessment of the anti-TF and -αGal antibodies level of the whole gastrointestinal group (n = 53), P = 0.002, HR = 0.25, 95% CI 0.094-0.655. In the follow-up, the survival time was shorter in patients whose level of anti-αGal antibodies rose (P = 0.009-0.040, HR = 2.18-4.27). The level of anti-TF antibodies inversely correlated with neutrophil/lymphocyte ratio (NLR, r = - 0.401, P = 0.004, n = 49). Patients with a higher level of anti-αGal antibodies and NLR values demonstrated a significantly worse survival (P = 0.009, HR = 2.98, n = 48).Conclusions: The preoperative levels of anti-TF, -Tn and -αGal antibodies and their dynamics are of prognostic significance. The method for the determination of circulating anti-carbohydrate antibodies may be a useful supplement in clinical outcome assessment.