Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases.
Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases.
复制标题
疾病特异性 IgG Fc N-糖基化作为个性化生物标志物，用于区分胃癌和良性胃病。
DOI：
10.1038/srep25957
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发表时间：
2016-05-13
影响因子：
4.6
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Zhang D;Chen B;Wang Y;Xia P;He C;Liu Y;Zhang R;Zhang M;Li Z
IgG片段可结晶（Fc）N-连接糖基化的病理生理作用的兴趣来自体液免疫应答的变化。本研究从443例良性胃疾病（BGD）和403例胃癌（GC）患者的846份血清中分离了来源于血清免疫炎症相关蛋白复合物的循环疾病特异性IgG（DSIGG），使用基质辅助激光解吸/电离分析在Asn 297位点处连接至IgG Fc区的DSIG糖肽。傅里叶变换离子回旋共振质谱（MALDI-FTICR MS）。共检测到22种糖肽。统计学分析表明，BGD患者中DSIGG 1 G1 S、DSIGG 2 G 0 F、G1、G2 F和G2 FS以及DSIGG 2半乳糖基化和唾液酸化与性别显著相关，并且DSIGG的年龄特异性糖型和糖基化特征在BGD患者和GC患者之间具有相似的变化趋势。此外，在两种病理生理状态之间也观察到来自DSIgG的半乳糖基化、唾液酸化和二等分N-乙酰葡糖胺（GlcNAc）的显著变化。受试者工作特征（ROC）分析表明，G2 FN/G1 FN（来自DSIgG 2）比值具有区分20-79岁女性BGD患者和女性GC患者的出色能力，灵敏度为82.6%，特异性为82.6%，曲线下面积（AUC）为0.872。
Interest in the pathophysiological role of IgG fragment crystallizable (Fc) N-linked glycosylation arose from changes in humoral immune responses. In this study, circulating disease-specific IgG (DSIgG) derived from serum immunoinflammation-related protein complexes was isolated from 846 serum samples of 443 patients with benign gastric diseases (BGDs) and 403 patients with gastric cancer (GC), and DSIgG glycopeptides attached to IgG Fc region at the site of Asn297 were analyzed using matrix-assisted laser desorption/ionization- Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). A total of 22 glycopeptides were detected. Statistical analysis indicated that DSIgG1 G1S, DSIgG2 G0F, G1, G2F, and G2FS as well as DSIgG2 galactosylation and sialylation are significantly associated with sex in BGD patients and that the age-specific glycoforms and glycosylation features from DSIgG between BGD patients and GC patients have similar change trends. In addition, significant changes in galactosylation, sialylation, and bisecting N-acetylglucosamine (GlcNAc) from DSIgG were also observed between two pathophysiological states. Receiver operating characteristic (ROC) analysis indicated that the G2FN/G1FN (from DSIgG2) ratio has an excellent capability to distinguish female BGD patients from female GC patients over the age range of 20–79 years, with the sensitivity of 82.6%, the specificity of 82.6%, and the area under curve (AUC) of 0.872.