N-linked glycan profiling in neuroblastoma cell lines.
N-linked glycan profiling in neuroblastoma cell lines.
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DOI：
10.1021/pr5011718
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发表时间：
2015-05-01
影响因子：
4.4
通讯作者：
Volchenboum SL
中科院分区：
文献类型：
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作者：
Hu Y;Mayampurath A;Khan S;Cohen JK;Mechref Y;Volchenboum SL
虽然MYCN扩增与侵袭性神经母细胞瘤有关，但区分低风险、MYCN非扩增神经母细胞瘤与高风险、MYCN扩增疾病的分子机制在很大程度上是未知的。基因组学和蛋白质组学研究在识别导致这种异质性的信号通路差异方面受到限制。N-连接糖基化是一种常见的蛋白质修饰，由糖与蛋白质残基的连接引起，并且在细胞信号传导和免疫应答中很重要。异常的N-连接糖基化通常与各种癌症有关。特别是，糖组学标记物通常已被证明可用于区分癌症与癌前状态。在此，我们对MYCN非扩增SY 5 Y和MYCN扩增NLF细胞系之间的N-连接糖组学变异进行了系统比较，目的是确定与高危神经母细胞瘤相关的糖丰度变化。通过液相色谱-质谱和生物信息学分析的组合，我们鉴定了16种聚糖，这些聚糖在NLF和SY 5 Y样品之间的丰度显示出统计学显著变化。更仔细的检查显示，与在MYCN非扩增样品中更占优势的较小的非唾液酸化聚糖相比，MYCN扩增样品中更大（就总单糖计数而言）和更多唾液酸化聚糖结构的偏好。这些结果为获得准确的神经母细胞瘤风险诊断的候选标记物提供了线索。
Although MYCN amplification has been associated with aggressive neuroblastoma, the molecular mechanisms that differentiate low-risk, MYCN-non amplified neuroblastoma from high-risk, MYCN-amplified disease are largely unknown. Genomic and proteomic studies have been limited in discerning differences in signaling pathways that account for this heterogeneity. N-linked glycosylation is a common protein modification resulting from the attachment of sugars to protein residues and important in cell signaling and immune response. Aberrant N-linked glycosylation has been routinely linked to various cancers. In particular, glycomic markers have often proved useful in distinguishing cancers from precancerous conditions. Here, we perform a systematic comparison of N-linked glycomic variation between MYCN-non-amplified SY5Y and MYCN-amplified NLF cell lines with the aim of identifying changes in sugar abundance linked to high-risk neuroblastoma. Through a combination of liquid chromatography-mass spectrometry and bioinformatics analysis, we identified 16 glycans that show a statistically significant change in abundance between NLF and SY5Y samples. Closer examination revealed the preference for larger (in terms of total monosaccharide count) and more sialylated glycan structures in the MYCN-amplified samples in comparison to smaller, non-sialylated glycans that are more dominant in the MYCN-non-amplified samples. These results offer clues for deriving marker candidates for accurate neuroblastoma risk diagnosis.