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结肠癌患者中抗-Thomsen - Friedenreich抗原抗体多样性的特征

Signatures of anti-Thomsen - Friedenreich antigen antibody diversity in colon cancer patients.

作者信息

Kurtenkov O, Bubina M, Klaamas K

机构信息

Department of Oncology and Immunology, National Institute for Health Development, Hiiu 42, Tallinn 11619, Estonia.

出版信息

Exp Oncol. 2018 Mar;40(1):48-58.

Abstract

AIM

To determine whether the structural and functional diversities of naturally occurring antibodies to the Thomsen - Friedenreich (TF) antigen may be of diagnostic and prognostic value in colon cancer.

MATERIALS AND METHODS

Serum samples were taken from patients with colon cancer (n = 94) and healthy controls (n = 64). The level of TF-specific antibody isotypes and their sialylation were determined using ELISA and lectin-ELISA with synthetic TF-polyacrylamide conjugate as an antigen and a sialic acid-specific Sambucus nigra agglutinin (SNA). The avidity was determined using ammonium thiocyanate as a chaotrope. The accuracy of diagnostics was evaluated using the receiver operator characteristic curve analysis and the survival analysis employing the Kaplan - Meier method.

RESULTS

Compared to healthy controls, patients with colon cancer exhibited a lower level of anti-TF IgG antibodies, significantly lower ratios of TF-specific IgG/IgM and IgG/IgA, an increased SNA reactivity of anti-TF antibodies, mostly on account of IgG, and a lower avidity of TF-specific antibodies, especially their SNA-reactive subset. An increased SNA reactivity of anti-TF IgG was observed already at the early stages of cancer (p = 0.0004). The decrease of the ratio of IgG/IgM and IgG/IgA showed a good accuracy of diagnostics with about 60% sensitivity at 90% specificity. A similar potential was found for the SNA binding/IgG level index. The high level of TF-specific IgA antibodies was associated with a lower survival rate (hazard ratio = 0.34).

CONCLUSION

This is the first report ever on the colon cancer-related signatures of anti-TF antibody diversity which show diagnostic potential, including in early cancer, and prognostic value. The hypersialylation of TF-specific antibodies appeared to be a common phenomenon in cancer. The signatures may be used as non-invasive antibody-based markers for colon cancer.

摘要

目的

确定针对桑德森-弗里登赖希(TF)抗原的天然存在抗体的结构和功能多样性是否对结肠癌具有诊断和预后价值。

材料与方法

采集结肠癌患者(n = 94)和健康对照者(n = 64)的血清样本。以合成的TF-聚丙烯酰胺偶联物为抗原,用ELISA和凝集素-ELISA结合唾液酸特异性黑接骨木凝集素(SNA)测定TF特异性抗体亚型水平及其唾液酸化情况。用硫氰酸铵作为离液剂测定亲和力。采用受试者工作特征曲线分析评估诊断准确性,并用Kaplan-Meier法进行生存分析。

结果

与健康对照者相比,结肠癌患者抗TF IgG抗体水平较低,TF特异性IgG/IgM和IgG/IgA比值显著降低,抗TF抗体的SNA反应性增加,主要是IgG,TF特异性抗体亲和力较低,尤其是其SNA反应性亚群。在癌症早期就观察到抗TF IgG的SNA反应性增加(p = 0.0004)。IgG/IgM和IgG/IgA比值的降低显示出良好的诊断准确性,在90%特异性时灵敏度约为60%。SNA结合/I gG水平指数也有类似潜力。TF特异性IgA抗体水平高与较低的生存率相关(风险比 = 0.34)。

结论

这是首篇关于抗TF抗体多样性与结肠癌相关特征的报告,这些特征显示出诊断潜力,包括在早期癌症中,以及预后价值。TF特异性抗体的高唾液酸化似乎是癌症中的常见现象。这些特征可作为基于抗体的结肠癌非侵入性标志物。

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