Breen Lucas D, Pučić-Baković Maja, Vučković Frano, Reiding Karli, Trbojević-Akmačić Irena, Šrajer Gajdošik Martina, Cook Madeleine I, Lopez Michael J, Wuhrer Manfred, Camara L M, Andjelković Uroš, Dupuy Damian E, Josić Djuro
Proteomics Core, COBRE CCRD, Rhode Island Hospital, Providence, RI, USA.
Genos Ltd., Glycobiology Research Laboratory, Zagreb, Croatia.
Biochim Biophys Acta. 2016 Aug;1860(8):1786-94. doi: 10.1016/j.bbagen.2016.01.011. Epub 2016 Jan 29.
Image-guided tumor ablation is a technique whereby needle-like applicators are placed directly into solid tumors under guidance typically with computed tomography or ultrasound. Changes in IgG and IgM antibody glycosylation were studied during ablation-induced immune response to cancer, and the use of glycosylation as a biomarker for diagnosis, prognosis and disease treatment was examined.
Plasma from 27 tumor patients was collected immediately before, after and for 6 months following ablation. IgG and IgM antibodies were isolated by use high-throughput chromatography, and analyzed by hydrophilic liquid chromatography. Thorough identification of glycan structures in each chromatography peak was performed by nano-liquid chromatography electrospray ionization mass spectrometry.
Although antibody glycosylation was found to vary with cancer type, discernable patterns of change based on the successful treatment of tumors by ablation were not identified. One patient with renal clear cell carcinoma and poor disease outcome had unexpectedly high amount of oligomannose IgG glycans during the whole period of monitoring. In contrast, IgM antibodies did not follow the same pattern.
These findings suggest that glycosylation patterns are indicative of an immune system that is unable to prevent different types of cancer, rather than products of the immunostimulatory response to the ablation of tumor itself. Analyses of the outcome effect suggested that IgG glycosylation and IgM glycosylation are not associated with tumor ablation.
Present work opens a new way for parallel determination of glycosylation changes of both IgG and IgM antibodies by use of high-throughput methods, and their future use as biomarkers for disease diagnosis and prognosis. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.
图像引导下的肿瘤消融是一种技术，在计算机断层扫描或超声引导下，将针状施源器直接插入实体肿瘤。研究了消融诱导的癌症免疫反应过程中IgG和IgM抗体糖基化的变化，并探讨了将糖基化用作诊断、预后和疾病治疗生物标志物的用途。
收集27例肿瘤患者在消融前、消融后及消融后6个月的血浆。通过高通量色谱法分离IgG和IgM抗体，并采用亲水液相色谱法进行分析。通过纳升液相色谱电喷雾电离质谱法对每个色谱峰中的聚糖结构进行全面鉴定。
虽然发现抗体糖基化因癌症类型而异，但未识别出基于消融成功治疗肿瘤的可辨别变化模式。一名肾透明细胞癌患者且疾病预后较差，在整个监测期间寡甘露糖IgG聚糖含量意外地高。相比之下，IgM抗体未呈现相同模式。
这些发现表明，糖基化模式表明免疫系统无法预防不同类型的癌症，而不是对肿瘤本身消融的免疫刺激反应产物。结果效应分析表明，IgG糖基化和IgM糖基化与肿瘤消融无关。
目前的工作开辟了一种新方法，可通过高通量方法并行测定IgG和IgM抗体的糖基化变化，以及它们未来用作疾病诊断和预后生物标志物的用途。本文是名为“个性化医学中的聚糖”特刊的一部分 客座编辑：戈尔丹·劳克教授。
