An Hyun Joo, Miyamoto Suzanne, Lancaster Katherine S, Kirmiz Crystal, Li Bensheng, Lam Kit S, Leiserowitz Gary S, Lebrilla Carlito B
Department of Chemistry, University of California-Davis Cancer Center, California 95616, USA.
J Proteome Res. 2006 Jul;5(7):1626-35. doi: 10.1021/pr060010k.
A glycomic approach is developed to identify oligosaccharide markers for ovarian cancer by rapidly profiling globally released oligosaccharides. Glycoproteins shed by cancer cells are found in the supernatant (or conditioned media) of cultured cells. In this approach, shed glycoproteins are profiled for their oligosaccharide content using beta-elimination conditions. Changes in glycosylation are monitored by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS). Because shed glycoproteins would also be found in serum, similar glycan profiling was performed to observe potential oligosaccharide markers. Oligosaccharide profiling data on a limited set of patient and normal serum samples were studied to determine potential glycan markers in ovarian cancer. We were able to demonstrate the presence of at least 15 unique serum glycan markers in all patients but absent in normal individuals. To determine the structure of the glycan biomarkers, a number of the ions were isolated and further analyzed using infrared multiphoton dissociation (IRMPD). One major advantage of this approach is that glycans are examined directly from patient sera without the need to obtain cancer biopsy specimens or to purify glycosylated proteins from these specimens.
通过对全局释放的寡糖进行快速分析，开发了一种糖组学方法来鉴定卵巢癌的寡糖标志物。癌细胞脱落的糖蛋白存在于培养细胞的上清液（或条件培养基）中。在这种方法中，使用β-消除条件对脱落的糖蛋白的寡糖含量进行分析。通过基质辅助激光解吸/电离傅里叶变换离子回旋共振质谱（MALDI-FTICR-MS）监测糖基化的变化。由于在血清中也会发现脱落的糖蛋白，因此进行了类似的聚糖分析以观察潜在的寡糖标志物。研究了一组有限的患者和正常血清样本的寡糖分析数据，以确定卵巢癌中的潜在聚糖标志物。我们能够证明所有患者中至少存在15种独特的血清聚糖标志物，而正常个体中不存在。为了确定聚糖生物标志物的结构，分离了一些离子，并使用红外多光子解离（IRMPD）进行进一步分析。这种方法的一个主要优点是可以直接从患者血清中检查聚糖，而无需获取癌症活检标本或从这些标本中纯化糖基化蛋白。
