Abundance-Ratio-Based Semiquantitative Analysis of Site-Specific N-Linked Glycopeptides Present in the Plasma of Hepatocellular Carcinoma Patients
Abundance-Ratio-Based Semiquantitative Analysis of Site-Specific N-Linked Glycopeptides Present in the Plasma of Hepatocellular Carcinoma Patients
复制标题
DOI：
10.1021/pr4011519
复制
发表时间：
2014-05-01
影响因子：
4.4
通讯作者：
Paik, Young-Ki
中科院分区：
文献类型：
--
作者：
Lee, Hyoung-Joo;Cha, Hyun-Jeong;Paik, Young-Ki
位点特异性 N 连接聚糖的异常结构与肝细胞癌 (HCC) 的肿瘤发生密切相关，肝细胞癌是全世界最常见的致命癌症之一。玻连蛋白 (VTN) 被认为是 HCC 的候选糖生物标志物。在这项研究中，我们描述了一种基于 VTN 位点特异性 N 连接糖肽丰度比的可靠且简单的定量策略，以筛选潜在的生物标志物。在 VTN 中存在的三个 N 连接位点（Asn-86、-169 和 -242）处表征了总共 14 个独特的 N 连接聚糖，对应于 27 个独特的 N 连接糖肽。这些聚糖可能是 HCC 的良好候选标志物。在这些聚糖中，两种代表性糖型（岩藻糖基与非岩藻糖基）的丰度比在 HCC 血浆中相对于正常血浆显着增加。该策略还成功应用于另一种潜在的 HCC 生物标志物触珠蛋白。此外，我们证明我们的方法采用串联质量标签（TMT）和 VTN 的目标 N 连接糖肽，是量化 HCC 血浆中相对于正常血浆的特定聚糖的有用工具。我们的策略代表了一个简单且可能有用的筛选平台，用于发现癌症特异性糖生物标志物
Aberrant structures of site-specific N-linked glycans are closely associated with the tumorigenesis of hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide. Vitronectin (VTN) is considered a candidate glycobiomarker of HCC. In this study, we describe a reliable and simple quantification strategy based on abundance ratios of site-specific N-linked glycopeptides of VTN to screen for potential biomarkers. A total of 14 unique N-linked glycans corresponding to 27 unique N-linked glycopeptides were characterized at three N-linked sites (Asn-86, -169, and -242) present in VTN. These glycans could be good candidate markers for HCC. Among these glycans, the abundance ratio of two representative glycoforms (fucosyl vs non-fucosyl) was significantly increased in HCC plasma relative to normal plasma. This strategy was also successfully applied to another potential HCC biomarker, haptoglobin. Furthermore, we demonstrate that our approach employing tandem mass tag (TMT) and target N-linked glycopeptides of VTN is a useful tool for quantifying specific glycans in HCC plasma relative to normal plasma. Our strategy represents a simple and potentially useful screening platform for the discovery of cancer-specific glycobiomarkers