Novel Glycan Biomarkers for the Detection of Lung Cancer
Novel Glycan Biomarkers for the Detection of Lung Cancer
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DOI：
10.1021/pr101034t
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发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Rudd, Pauline M.
中科院分区：
文献类型：
--
作者：
Arnold, James N.;Saldova, Radka;Rudd, Pauline M.
肺癌预后差，5年生存率为15%。因此，早期发现至关重要。血清癌症相关生物标志物的诊断检测是一种无创检测方法。糖基化是蛋白质翻译后最常见的修饰，它已被证明在癌症中发生改变。在本文中，高通量HILIC技术应用于100名肺癌患者的血清样本，以及84名年龄匹配的对照组，并鉴定了n -链糖基化的显著改变。在含有Sialyl Lewis X的聚糖、单触角聚糖、高度唾液化的聚糖中检测到增加，而在核心聚焦的双触角聚糖中观察到减少，其中一些早在i期就可以检测到。触珠蛋白的n链聚糖谱显示出与血清总糖相似的变化。肺癌样本中最显著改变的HILIC峰主要包括二二化和三、四天线聚糖。与对照组相比，这一潜在疾病标志物在所有疾病组中都显著增加，即使将吸烟的影响考虑在内，也能看到强烈的疾病影响。所有糖生物标志物联合使用具有最高的敏感性和特异性。本研究确定了作为该疾病潜在生物标志物的候选物，有待进一步研究。
Lung cancer has a poor prognosis and a 5-year survival rate of 15%. Therefore, early detection is vital. Diagnostic testing of serum for cancer-associated biomarkers is a noninvasive detection method. Glycosylation is the most frequent post-translational modification of proteins and it has been shown to be altered in cancer. In this paper, high-throughput HILIC technology was applied to serum samples from 100 lung cancer patients, alongside 84 age-matched controls and significant alterations in N-linked glycosylation were identified. Increases were detected in glycans containing Sialyl Lewis X, monoantennary glycans, highly sialylated glycans and decreases were observed in core-fucosylated bi-antennary glycans, with some being detectable as early as in Stage I. The N-linked glycan profile of haptoglobin demonstrated similar alterations to those elucidated in the total serum glycome. The most significantly altered HILIC peak in lung cancer samples includes predominantly disialylated and tri- and tetra-antennary glycans. This potential disease marker is significantly increased across all disease groups compared to controls and a strong disease effect is visible even after the effect of smoking is accounted for. The combination of all glyco-biomarkers had the highest sensitivity and specificity. This study identifies candidates for further study as potential biomarkers for the disease.