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血浆免疫球蛋白G糖基化与结直肠癌预后

Glycosylation of plasma IgG in colorectal cancer prognosis.

作者信息

Theodoratou Evropi, Thaçi Kujtim, Agakov Felix, Timofeeva Maria N, Štambuk Jerko, Pučić-Baković Maja, Vučković Frano, Orchard Peter, Agakova Anna, Din Farhat V N, Brown Ewan, Rudd Pauline M, Farrington Susan M, Dunlop Malcolm G, Campbell Harry, Lauc Gordan

机构信息

The Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.

Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and Medical Research Council Human Genetics Unit, Crewe Road, Edinburgh, EH4 2XU, UK.

出版信息

Sci Rep. 2016 Jun 15;6:28098. doi: 10.1038/srep28098.

Abstract

In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glycan structures were strongly associated with all-cause (q < 0.01) and CRC mortality (q = 0.04 for galactosylation and sialylation). Clinical algorithms showed good prediction of all-cause and CRC mortality (Harrell's C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). The inclusion of IgG glycan data did not lead to any statistically significant improvements overall, but it improved the prediction over clinical models for stage 4 patients with the shortest follow-up time until death, with the median gain in the test AUC of 0.08. These glycan differences are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. In the absence of validated biomarkers to improve upon prognostic information from existing clinicopathological factors, the potential of these novel IgG glycan biomarkers merits further investigation.

摘要

在本研究中,我们证明了免疫球蛋白G(IgG)糖基化作为结直肠癌(CRC)一种新型预后生物标志物的潜在价值。我们分析了1229例CRC患者的血浆IgG聚糖,并将其与生存结果相关联。我们评估了临床算法的预测价值,并将其与还包括聚糖预测因子的算法进行比较。IgG聚糖结构中半乳糖基化降低、唾液酸化降低(岩藻糖基化IgG聚糖结构的)以及平分型N-乙酰葡糖胺增加与全因死亡率(q < 0.01)和CRC死亡率(半乳糖基化和唾液酸化的q = 0.04)密切相关。临床算法对全因和CRC死亡率显示出良好的预测能力(Harrell's C:0.73,0.77;AUC:0.75,0.79;IDI:分别为0.02,0.04)。总体而言,纳入IgG聚糖数据并未带来任何统计学上的显著改善,但对于随访时间最短直至死亡的4期患者,它比临床模型改善了预测,测试AUC的中位数增益为0.08。这些聚糖差异与IgG促炎活性显著增加与较差的CRC预后相关一致,尤其是在晚期CRC中。在缺乏经过验证的生物标志物以改善现有临床病理因素的预后信息的情况下,这些新型IgG聚糖生物标志物的潜力值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae33/4908421/5c762759457d/srep28098-f1.jpg

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