Department of Chemistry, University of California, Davis, CA, USA.
J Chromatogr A. 2013 Mar 1;1279:58-67. doi: 10.1016/j.chroma.2012.12.079. Epub 2013 Jan 11.
Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we analyzed and compared serum samples from epithelial ovarian cancer cases (n=46) and healthy control individuals (n=48). Over 250 N-linked glycan compound peaks with over 100 distinct N-linked glycan compositions were identified. Statistical testing identified 26 potential glycan biomarkers based on both compositional and structure-specific analyses. Using these results, an optimized model was created incorporating the combined abundances of seven potential glycan biomarkers. The receiver operating characteristic (ROC) curve of this optimized model had an area under the curve (AUC) of 0.96, indicating robust discrimination between cancer cases and healthy controls. Rapid-throughput chromatographic glycan profiling was found to be an effective platform for structure-specific biomarker discovery.
几十年来，在几乎所有类型的癌症中都观察到了异常的糖基化，现在它已被充分确立为致癌的指标。然而，为了从糖组中挖掘生物标志物，需要能够快速分离、鉴定和定量异构聚糖的分析方法。我们已经开发了一种使用基于微流控芯片的纳流液相色谱（nano-LC）/质谱进行色谱糖组学分析的快速高通量方法。为了证明该方法的实用性，我们分析并比较了上皮性卵巢癌病例（n=46）和健康对照个体（n=48）的血清样本。鉴定出超过 250 个 N-连接聚糖化合物峰，具有超过 100 种不同的 N-连接聚糖组成。基于组成和结构特异性分析，统计测试确定了 26 个潜在的聚糖生物标志物。使用这些结果，创建了一个包含七个潜在聚糖生物标志物的组合丰度的优化模型。该优化模型的接收器操作特性（ROC）曲线的曲线下面积（AUC）为 0.96，表明癌症病例和健康对照之间有很强的区分能力。快速高通量色谱糖组学分析被发现是一种用于结构特异性生物标志物发现的有效平台。
