National Institute for Health Development, Hiiu, Tallinn, Estonia.
Glycoconj J. 2012 Jan;29(1):57-66. doi: 10.1007/s10719-011-9364-z. Epub 2011 Dec 17.
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.
IgG Fc 糖基强烈影响 Fcγ 受体相互作用和 Fc 介导的效应机制。IgG 糖基结构的变化与各种疾病相关，如感染和自身免疫。然而，Fc 糖基在肿瘤免疫中的可能作用尚未完全了解。本研究旨在使用 LC-ESI-MS 方法分析 80 例胃癌患者和 51 例对照 IgG 样本的 Fc N-糖基，将结果与癌症分期和患者生存相关联。分析 32 种不同的 IgG N-糖基发现，癌症患者中去半乳糖基化（GnGnF、GnGn(bi)F）和半乳糖基化（AGn(bi)、AGn(bi)F、AA(bi)、AAF）以及单唾液酸化 IgG 糖型（NaAF、NaA(bi)）的含量显著增加。在肿瘤分期 II 和 III 中观察到 Fc 岩藻糖基化的统计学显著增加，而双分支 GlcNAc 的存在则出现相反的变化。完全唾液酸化糖的水平升高和具有双分支 GlcNAc 的糖的表达升高与更好的生存率相关。我们的研究结果首次提供了证据，表明 Fc 聚糖谱的变化可能预测胃癌患者的生存。Fc 岩藻糖基化和双分支 N-乙酰葡萄糖胺表达的癌症分期依赖性变化以及几种 IgG 糖型与生存的关联表明，IgG 糖基化与癌症的发病机制和疾病进展有关。
