Xu Tingting, Huang Jianmin, Lin Jiajing, Liu Yuanyuan, Wang Yi, Shen Wenkang, He Jianjie, Chen Shuyun, Zhu Xi, Que Yuqin, Hu Mengting, Chen Yu, Cheng Liming, He Honghao, Liu Xin, Liu Si
Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350122, China.
Digestive Endoscopy Center, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350000, China.
BMC Cancer. 2025 Feb 7;25(1):217. doi: 10.1186/s12885-025-13616-z.
The relationship between cancer development and alterations in IgG N-glycosylation has been well-established. However, comprehensive profiling of the N-glycome and N-glycoproteome in gastric cancer (GC) remains limited. Furthermore, the prognostic potential of IgG N-glycan patterns in identifying precursors to GC has yet to be fully elucidated.
The IgG N-glycome in GC was characterized using a custom high-throughput orthogonal mass spectrometry approach. Multivariate analysis was employed to identify and assess glycomic alterations. A comprehensive bioinformatics analysis was also conducted to investigate the differential expression of N-glycosylation-related genes and their potential roles in GC pathogenesis. Additionally, interleukin-11 (IL-11) levels were quantified using a standardized enzyme-linked immunosorbent assay (ELISA).
Galactosylation and sialylation of IgG decreased mainly in the IgG1 and IgG2 subclasses in GC, with subclass-specific changes in IgG3 and IgG4 galactosylation. These glycan modifications were represented by unique glycopeptides (IgG1_H5N5, IgG2_H4N3F1, IgG2_H4N4, IgG2_H4N4F1S1, IgG3/4_H4N4F1, IgG3/4_H4N4F1S1), which outperformed CA72-4 for GC diagnosis. Analysis of key glycogenes revealed differential expression patterns, implicating a functional role for IgG N-glycosylation in GC. Notably, the abundance of specific IgG glycosylation exhibited a significant correlation with serum level of IL-11.
Alterations in subclass-specific IgG N-glycosylation represent promising biomarkers for the detection and monitoring of GC progression, potentially influenced by cytokine-driven inflammation. Understanding these changes could improve our knowledge of molecular mechanisms, aiding in diagnostic improvements and therapeutic development.
癌症发展与IgG N-糖基化改变之间的关系已得到充分证实。然而，胃癌（GC）中N-聚糖组和N-糖蛋白组的全面分析仍然有限。此外，IgG N-聚糖模式在识别GC前体方面的预后潜力尚未完全阐明。
采用定制的高通量正交质谱方法对GC中的IgG N-聚糖组进行表征。采用多变量分析来识别和评估糖组学改变。还进行了全面的生物信息学分析，以研究N-糖基化相关基因的差异表达及其在GC发病机制中的潜在作用。此外，使用标准化酶联免疫吸附测定（ELISA）对白细胞介素-11（IL-11）水平进行定量。
GC中IgG的半乳糖基化和唾液酸化主要在IgG1和IgG2亚类中降低，IgG3和IgG4半乳糖基化存在亚类特异性变化。这些聚糖修饰由独特的糖肽（IgG1_H5N5、IgG2_H4N3F1）表示，IgG2_H4N4、IgG2_H4N4F1S1、IgG3/4_H4N4F1、IgG3/4_H4N4F1S1），其在GC诊断方面优于CA72-4。对关键糖基因的分析揭示了差异表达模式，表明IgG N-糖基化在GC中具有功能作用。值得注意的是，特定IgG糖基化的丰度与血清IL-11水平呈显著相关。
亚类特异性IgG N-糖基化的改变代表了用于检测和监测GC进展的有前景的生物标志物，可能受细胞因子驱动的炎症影响。了解这些变化可以提高我们对分子机制的认识，有助于改进诊断和治疗开发。
