Multidimensional liquid chromatography platform for profiling alterations of clusterin N-glycosylation in the plasma of patients with renal cell carcinoma.
Multidimensional liquid chromatography platform for profiling alterations of clusterin N-glycosylation in the plasma of patients with renal cell carcinoma.
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DOI：
10.1016/j.chroma.2012.07.066
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发表时间：
2012-09-21
期刊：
影响因子：
--
通讯作者：
Hincapie M
中科院分区：
文献类型：
--
作者：
Tousi F;Bones J;Iliopoulos O;Hancock WS;Hincapie M
识别现有癌症生物标志物糖基化的潜在变化可提高诊断的敏感性和特异性。簇集蛋白（载脂蛋白J）作为潜在生物标志物与肾细胞癌（RCC）及其他类型的恶性肿瘤有关。在本研究中，开发了一种自动化多维高效液相色谱平台，能够从血浆样本中高通量亲和富集簇集蛋白。结合二维凝胶电泳，分离出了微克级的高纯度簇集蛋白，适用于聚糖表征。该分析平台被应用于一小群肾切除术前和术后的肾细胞癌患者，以研究簇集蛋白糖基化，作为一项初步研究来评估该平台的性能。在术后血浆样本中，观察到双触角二半乳糖基二唾液酸化（A2G2S(3)2）聚糖水平显著降低，而核心岩藻糖基化双触角二半乳糖基二唾液酸化聚糖（FA2G2S(6)2）和三触角三半乳糖基二唾液酸化聚糖（A3G3S(6)2）水平升高。
Identification of potential changes in the glycosylation of existing cancer biomarkers can result in a higher level of diagnostic sensitivity and specificity. Clusterin (Apolipoprotein J) has been implicated in renal cell carcinoma (RCC) and other types of malignancy as potential biomarker. In the present work, an automated multidimensional HPLC platform enabling high throughput affinity enrichment of clusterin from plasma samples was developed. Integrated with two dimensional gel electrophoresis, high purity clusterin in microgram quantities suitable for glycan characterization was isolated. The analytical platform was applied to study clusterin glycosylation in a small group of RCC patients before and after nephrectopy as a pilot study to evaluate the performance of the platform. A statistically significant decrease was observed in the levels of a bi-antennary digalactosyl disialylated (A2G2S(3)2) glycans while the levels of a core fucosylated bi-antennary digalactosyl disialylated glycan (FA2G2S(6)2) and a tri-antennary trigalactosyl disialylated glycan (A3G3S(6)2) were increased in the post-surgery plasma samples.
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影响因子：
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