The Relation of the Level of Serum Anti-TF, -Tn and -Alpha-Gal IgG to Survival in Gastrointestinal Cancer Patients

Abstract

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.

Signatures of Anti-Thomsen — Friedenreich Antigen Antibody Diversity in Colon Cancer Patients

“…Besides, changes of some parameters, such as IgG/IgM and IgA/IgM ratios and SNA/IgG index, revealed a good diagnostic accuracy at the early stages of colon cancer and can be used as novel diagnostic biomarkers. The anti-TF IgG level was associated with a better survival, which was in accordance with previously reported findings in patients with gastrointestinal or breast cancer [18][19][20][40][41][42]. In order to establish whether the relative proportions of different anti-TF antibody isotypes have diagnostic and/or prognostic value, we attempted to establish the ratio between the levels of TF-specific IgG, IgM and IgA antibodies at different stages of colon cancer.…”

“…Having altered post-translational modifications and/or aberrantly expressed, tumorassociated glycans can trigger an immune response [1,2,10,33]. Naturally occurring antibodies to tumorassociated glycans, including the TF glycotope, were shown to participate in antibodies-mediated tumor defence, and their level was associated with tumor progression, metastases, and patients survival [7,8,[18][19][20]. A common trend towards the decrease of the level of natural anti-TF antibody in serum was found in cancer patients [12,13,41].…”

“…Anti-TF antibody and TF-specific lectins have been shown to inhibit cancer cell proliferation and metastasis in TF expressing cells [14][15][16]. Clinically and experimentally observed prognostic improvements in cancer patients with a high level of TF-specific IgG antibodies indicate that the TF-specific innate and/or adaptive immune response is an important part of cancer immunosurveillance, and TF antigen is a promising target for cancer immunotherapy [17][18][19][20][21][22]. However, the clinical role of the diversity parameters of TF-specific antibodies, including glycosylation and functional activity, remains yet unclear.…”

Increased Avidity of theSambucus nigraLectin-Reactive Antibodies to the Thomsen-Friedenreich Antigen as a Potential Biomarker for Gastric Cancer

“…It has been shown that various Ab glycoforms display different effector functions and determine the activity of antibodies against tumors [ 5 , 39 – 41 ]. Previous studies have demonstrated that naturally occurring antibodies to tumor associated glycans are involved in natural tumor immunity, being associated with tumor progression and cancer patients survival [ 18 , 26 , 42 , 43 ]. Natural anti-TF antibodies (Abs) of different isotypes (IgG, IgM, and IgA) are present in each individual thus making these antibodies a convenient target for analysis, in contrast to tumor-derived products that may be detected in a minority of patients due to their extreme dilution in the circulation and rapid degradation or clearance.…”

Hidden IgG Antibodies to the Tumor-Associated Thomsen-Friedenreich Antigen in Gastric Cancer Patients: Lectin Reactivity, Avidity, and Clinical Relevance

“…Instead, a decrease in the level of serum TF-specific Abs is usually observed [9–11, 13]. However, no data still exist on the possible involvement of any particular subset of anti-TF IgG Abs in this decrease.…”