Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients
Serum protein profiling by SELDI mass spectrometry: detection of multiple variants of serum amyloid alpha in renal cancer patients
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DOI：
10.1038/labinvest.3700097
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发表时间：
2004-07-01
影响因子：
5
通讯作者：
Flad, T
中科院分区：
文献类型：
--
作者：
Tolson, J;Bogumil, R;Flad, T
血清的分子分析是定义潜在诊断标志物或疾病相关蛋白质改变的重要领域。新型蛋白质组学技术，例如基于质谱的表面增强激光解吸/电离 (SELDI) ProteinChip(R) 技术，有助于对此类蛋白质混合物进行快速且可重复的分析，并为研究人员寻找疾病生物标志物提供了新的维度。在这里，我们将这项技术应用于研究一组来自明确特征的肾细胞癌患者的血清样本，通过与健康对照进行比较来鉴定此类蛋白质。除了尚未鉴定的 10.84 kDa 标记物之外，我们还检测并鉴定了触珠蛋白 1a 和血清淀粉样蛋白 α-1 (SAA-1) 与疾病相关。特别值得注意的是多重检测中 SAA-1 的多种变体，这些变体在癌症患者的血清中尚未描述过。 SELDI 将 SAA-1 检测为 N 末端的全长蛋白、脱精氨酸和脱精氨酸/脱丝氨酸变体。此外，我们还可以检测到减去前五个 N 端氨基酸的低丰度变体。此类变异可能会影响蛋白质的功能。我们得出的结论是，该技术是一种可重复、快速且简单的模式，用于发现和分析血清中疾病的标记蛋白。
The molecular analysis of serum is an important field for the definition of potential diagnostic markers or disease-related protein alterations. Novel proteomic technologies such as the mass spectrometric-based surface-enhanced laser desorption/ionization (SELDI) ProteinChip(R), technique facilitate a rapid and reproducible analysis of such protein mixtures and affords the researcher a new dimension in the search for biomarkers of disease. Here, we have applied this technology to the study of a cohort of serum samples from well-characterized renal cell carcinoma patients for the identification of such proteins by comparison to healthy controls. We detected and characterized haptoglobin 1 a and serum amyloid alpha-1 (SAA-1) as disease related, in addition to an as-yet-unidentified marker of 10.84 kDa. Of particular note is the detection of multiple variants of SAA-1 in multiplex that have not been described in the sera of cancer patients. SAA-1 is detected as full-length protein, des-Arginine and des-Arginine/des-Serine variants at the N terminus by SELDI. In addition, we could also detect a low-abundant variant minus the first five N-terminal amino acids. Such variants may impact the function of the protein. We conclude the technique to be a reproducible, fast and simple mode for the discovery and analysis of marker proteins of disease in serum.