The development of mass spectrometry for Clinical Glycomics

描述(由申请人提供)：我们将开发方法和工具来分析人体体液中的葡聚糖，以便发现疾病的标志物。癌症是一种已知的伴随异常糖基化的疾病。疾病细胞脱落的糖蛋白将被收获，以确定其糖蛋白含量，并对其进行分析，以获得疾病标志物。这种方法代表了疾病标记物发现的新范例。它将主要关注作为疾病标志物的葡聚糖，而忽略了最初相关蛋白质的特性。这种方法将是多方面的，主要是以糖为中心的；它对比和补充了目前正在进行广泛研究的以蛋白质组为中心的方法。在这个过程中，我们将开发一套基于质谱学的临床糖组学工具。这些工具将被用来观察两种人体液体--血清和泪液中疾病的糖基化变化。这些液体是根据我们的合作者在包括卵巢癌和眼部酒渣鼻在内的疾病中的需求而选择的，但对于血清和其他干眼病的泪液将直接影响乳腺癌和前列腺癌。虽然疾病标记物将是这些研究的未来结果，但它们不会是该项目的唯一重点。相反，我们还将开发我们的合作者将使用的工具，以发现这些疾病的标志物，并为临床使用质谱学进行血糖分析奠定基础。

DESCRIPTION (provided by applicant): We will develop the methods and tools that will profile glycans in human fluids to enable the discovery of markers for diseases. Cancer is a disease known to accompany aberrant glycosylation. Glycoproteins shed by diseased cells will be harvested for their glycan content and profiled to obtain disease markers. This approach represents a new paradigm for disease marker discovery. It will focus primarily on the glycans as disease markers while neglecting, at first, the identity of the associated proteins. This approach will be multifaceted and primarily glycocentric; it contrasts and complements the proteome-centered approaches currently under extensive investigations. In this process, we will develop a set of mass spectrometry-based tools for clinical glycomics. These tools will be used to observe changes in glycosylation of diseases in two human fluids, sera and tear. The fluids are chosen by the needs of our collaborator in diseases that include ovarian cancer and ocular rosacea but will have direct implications in breast cancer and prostate cancer for sera and other dry eye diseases for tear fluids. While disease markers will be the future outcome of these studies, they will not be the only focus of this project. Instead we will also develop the tools that will be used by our collaborators to discover markers for these diseases and lay the foundation for the use of mass spectrometry in clinics for glycomic analyses.