Serum N-glycome alterations in colorectal cancer associate with survival.
Serum N-glycome alterations in colorectal cancer associate with survival.
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DOI：
10.18632/oncotarget.25753
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发表时间：
2018-07-17
期刊：
影响因子：
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通讯作者：
Wuhrer M
中科院分区：
文献类型：
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作者：
de Vroome SW;Holst S;Girondo MR;van der Burgt YEM;Mesker WE;Tollenaar RAEM;Wuhrer M
蛋白质在临床实验室中进行常规测量，用于诊断、预后和治疗监测。然而，测试改进（性能）和创新（生物标志物）都是需要的，蛋白质N-糖基化提供了丰富的潜在标志物来源。在这里，我们分析了总血清N-糖组在匹配的病例对照研究（124例与124对照）的结直肠癌患者。这些结果在一个独立的样本队列（61例病例与61例对照）中得到验证，并在治愈患者的术后样本中进行了进一步测试。我们的结果揭示了患者和对照之间的显著差异，与来自对照的血清中主要是双触角N-聚糖相比，结肠直肠癌患者血清中N-聚糖的大小（触角）和唾液酸化增加。此外，聚糖改变与癌症分期和生存率有很强的相关性：血清N-糖组改变的患者（46%）和N-糖组与对照组相似的患者（87%）之间的五年生存率差异很大。重要的是，总血清N-糖组显示出超出年龄和分期的预后价值。这项临床糖组学研究提供了新的血清生物标志物候选物，并显示了血清总N-聚糖作为预后组的潜力。此外，如术前和术后样本所示，成功治疗后血清N-糖组变化恢复至对照样曲线。
Proteins are routinely measured in clinical laboratories for diagnosis, prognosis and therapy monitoring. Nevertheless, both test improvements (performance) and innovations (biomarkers) are needed, and protein N-glycosylation offers a rich source of potential markers. Here, we have analyzed the total serum N-glycome in a matched case-control study (124 cases versus 124 controls) of colorectal cancer patients. The results were validated in an independent sample cohort (both 61 cases versus 61 controls) and further tested in post-operative samples of cured patients. Our results revealed significant differences between patients and controls, with increased size (antennae) and sialylation of the N-glycans in the colorectal cancer patient sera as compared to mainly di-antennary N-glycans in sera from controls. Furthermore, glycan alterations showed strong associations with cancer stage and survival: The five-year survival rate largely varied between patients with an altered serum N-glycome (46%) and an N-glycome similar to controls (87%). Importantly, the total serum N-glycome showed prognostic value beyond age and stage. This clinical glycomics study provides novel serum biomarker candidates and shows the potential of total serum N-glycans as a prognostic panel. Moreover, serum N-glycome changes reverted to a control-like profile after successful treatment as was demonstrated from pre- and post-operative samples.