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Comprehensive analysis of human IgG Fc N-glycopeptides and construction of a screening model for colorectal cancer.
Journal of Proteomics ( IF 3.3 ) Pub Date : 2019-12-14 , DOI: 10.1016/j.jprot.2019.103616
Yang Zou 1 , Jianxing Hu 2 , Jianzheng Jie 3 , Junyong Lai 2 , Mingna Li 2 , Zhenming Liu 2 , Xiajuan Zou 4
Affiliation  

Currently, analyzing intact glycopeptides remains a challengeable task. Considerable progress has been achieved in the knowledge of immunoglobulin G (IgG) glycans in patients with colorectal cancer (CRC), whereas data on IgG Fc N-glycopeptides are scarce in the literature. To fill this gap in knowledge, we developed a rapid and effective method to obtain and analyze IgG Fc N-glycopeptides in the plasma from 46 CRC patients and 67 healthy individuals using chitosan@poly (glycidyl methacrylate) @iminodiacetic acid (CS@PGMA@IDA) nanomaterial in combination with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). A total of 29 N-glycopeptides were detected and analyzed. Compared with healthy individuals, CRC patients had increased levels of N-acteylglucosamine, yet decreased levels of galactosylation, fucosylation and sialylation. Further, a multivariate logistic regression model was developed using the levels of IgG Fc N-glycopeptides to distinguish CRC patients from healthy individuals, and the prediction performance was good, with an average AUC of the ROC curves of 0.893. SIGNIFICANCE: In this study, we proposed a strategy for obtaining and analyzing IgG glycopeptides using CS@PGMA@IDA nanomaterial in combination with MALDI-TOF-MS. Using this strategy, IgG Fc N-glycopeptides were analyzed in the plasma of CRC patients, and our findings indicated that glycosylation levels in the IgG Fc region were closely related to CRC. By using the IgG N-glycopeptide enrichment method and screening model designed in this study, early large-scale colorectal cancer screening can be implemented easily and fast.

中文翻译:

人IgG Fc N-糖肽的全面分析和大肠癌筛查模型的构建。

目前,分析完整的糖肽仍然是一项艰巨的任务。在结直肠癌(CRC)患者的免疫球蛋白G(IgG)聚糖知识方面已经取得了相当大的进展,而文献中缺乏关于IgG Fc N-糖肽的数据。为了填补这一知识空白,我们开发了一种快速有效的方法,使用壳聚糖@聚(甲基丙烯酸缩水甘油酯)@亚氨基二乙酸(CS @ PGMA @)从46位CRC患者和67位健康个体的血浆中获取和分析IgG Fc N-糖肽。 IDA)纳米材料,结合基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)。总共检测和分析了29种N-糖肽。与健康个体相比,CRC患者的N-乙酰葡萄糖胺水平升高,但半乳糖基化水平降低,岩藻糖基化和唾液酸化。此外,使用IgG Fc N-糖肽的水平建立了多元logistic回归模型,以区分CRC患者与健康个体,并且预测性能良好,ROC曲线的平均AUC为0.893。意义:在这项研究中,我们提出了一种使用CS @ PGMA @ IDA纳米材料结合MALDI-TOF-MS来获得和分析IgG糖肽的策略。使用这种策略,对CRC患者血浆中的IgG Fc N-糖肽进行了分析,我们的发现表明IgG Fc区的糖基化水平与CRC密切相关。通过使用本研究中设计的IgG N-糖肽富集方法和筛选模型,可以轻松,快速地进行早期大规模大肠癌的筛选。使用IgG Fc N-糖肽水平建立多变量logistic回归模型,将CRC患者与健康个体区分开,并且预测性能良好,ROC曲线的平均AUC为0.893。意义:在这项研究中,我们提出了一种使用CS @ PGMA @ IDA纳米材料结合MALDI-TOF-MS来获得和分析IgG糖肽的策略。使用这种策略,对CRC患者血浆中的IgG Fc N-糖肽进行了分析,我们的发现表明IgG Fc区的糖基化水平与CRC密切相关。通过使用本研究中设计的IgG N-糖肽富集方法和筛选模型,可以轻松,快速地进行早期大规模大肠癌的筛选。使用IgG Fc N-糖肽水平建立多变量logistic回归模型,将CRC患者与健康个体区分开,并且预测性能良好,ROC曲线的平均AUC为0.893。意义:在这项研究中,我们提出了一种使用CS @ PGMA @ IDA纳米材料结合MALDI-TOF-MS来获得和分析IgG糖肽的策略。使用这种策略,对CRC患者血浆中的IgG Fc N-糖肽进行了分析,我们的发现表明IgG Fc区的糖基化水平与CRC密切相关。通过使用本研究中设计的IgG N-糖肽富集方法和筛选模型,可以轻松,快速地进行早期大规模大肠癌的筛选。
更新日期:2019-12-17
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