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血清免疫球蛋白G N-聚糖组:子宫内膜癌的一种潜在生物标志物。

Serum immunoglobulin G N-glycome: a potential biomarker in endometrial cancer.

作者信息

Lin Sihan, Wang You, Wang Xinran, Yan Bin, Lou Weihua, Di Wen

机构信息

Department of Obstetrics and Gynecology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, China.

出版信息

Ann Transl Med. 2020 Jun;8(12):748. doi: 10.21037/atm-20-3504.

Abstract

BACKGROUND

With the increase in incidence and mortality of endometrial cancer (EC), there is an urgent need to explore non-invasive strategies for identifying EC patients and facilitating risk stratification. The alteration of immunoglobulin G (IgG) N-glycome has been indicated in autoimmune diseases and several cancer types, demonstrating a significant association with disease pathogenesis and progression. However, little has been investigated in the IgG N-glycome of EC patients.

METHODS

A total of 94 EC patients and 112 healthy females were recruited and sorted into an EC cohort and a control cohort. Serum samples were obtained from every participant, and IgG N-glycome profiling was conducted using ultra-performance liquid chromatography (UPLC).

RESULTS

A total of 24 directly measured N-glycans and 11 derived traits based on the shared glycan structures were analyzed in the EC and control cohorts. We detected a significant downregulation of galactosylation and sialylation in the EC cohort compared with the control cohort, while glycans with bisecting N-acetylglucosamine (GlcNAc) were elevated in EC patients. Receiver operating characteristic (ROC) analysis based on glycan traits showed good diagnostic performance of IgG N-glycans for EC. Furthermore, by exploring the association of IgG N-glycome with prognostic risk factors in EC, we observed that lower levels of galactosylation and sialylation were correlated with high-risk factors including older age, non-endometrioid histologic subtypes, advanced stage, poor differentiation of tumor, and >50% myometrial invasion (MI).

CONCLUSIONS

Our results suggest that the IgG N-glycome profile could be a potential biomarker for EC diagnosis and a promising indicator for prognostic risk factors, and thus may facilitate the early detection of EC and the identification of high-risk patients.

摘要

背景

随着子宫内膜癌(EC)发病率和死亡率的上升,迫切需要探索用于识别EC患者和促进风险分层的非侵入性策略。免疫球蛋白G(IgG)N-聚糖的改变已在自身免疫性疾病和几种癌症类型中得到证实,表明与疾病的发病机制和进展存在显著关联。然而,关于EC患者IgG N-聚糖的研究较少。

方法

共招募了94例EC患者和112名健康女性,并将其分为EC队列和对照队列。从每位参与者获取血清样本,并使用超高效液相色谱(UPLC)进行IgG N-聚糖谱分析。

结果

在EC队列和对照队列中分析了总共24种直接测量的N-聚糖和基于共享聚糖结构的11种衍生特征。与对照队列相比,我们检测到EC队列中半乳糖基化和唾液酸化显著下调,而具有平分N-乙酰葡糖胺(GlcNAc)的聚糖在EC患者中升高。基于聚糖特征的受试者操作特征(ROC)分析显示IgG N-聚糖对EC具有良好的诊断性能。此外,通过探索IgG N-聚糖与EC预后风险因素的关联,我们观察到较低水平的半乳糖基化和唾液酸化与包括年龄较大、非子宫内膜样组织学亚型、晚期、肿瘤分化差和>50%肌层浸润(MI)在内的高危因素相关。

结论

我们的结果表明,IgG N-聚糖谱可能是EC诊断的潜在生物标志物和预后风险因素的有前景指标,因此可能有助于EC的早期检测和高危患者的识别。

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