Early Cancer Detection & Prognosis through Glycomics

描述（由申请人提供）：我们不是寻找特定的癌症生物标志物（蛋白质或糖基化蛋白质），而是强调在未分离的生物样品中定量去糖基化（去除聚糖），并在定量聚糖图中显示去除的聚糖。比较来自健康和患病个体的糖糖谱，可以确定与癌症相关的结构变化。另一方面，预后或对患者健康的鉴别评估依赖于同位素辅助的定量质谱测量。在我们提出的研究的前两个阶段，临床相关样品将通过我们完善的程序进行筛选，同时使用最先进的MS-based方法和毛细管电泳。在第一阶段，将收集健康女性和男性的血清糖糖模式与卵巢癌、前列腺癌、肺癌和结肠癌患者的血清糖糖模式进行比较。通过生物信息学和统计学评估，将确定与每一种癌症或所有待研究癌症相关的聚糖标记物清单。这对于建立糖基化或“糖基化畸变”发生的定量趋势，并将这些测量结果与积极识别的聚糖结构联系起来是必要的。通过CE-LIF获得的相同样品的糖偶联图谱将有助于确定由于结构异构体的变化而导致的变化，这是通过ms无法确定的。在第二阶段，将比较使用特定药物治疗前后的人类癌症血清糖偶联图谱。在这一阶段，将密切监测1期确定的一组聚糖的变化，并评估它们因癌症进展或缓解而发生的变化。ii期结果将证实或驳斥将在i期被定义为潜在生物标志物的潜在聚糖结构。在确定这些特定的聚糖变化或由于疾病进展或缓解而改变的一组聚糖结构后，将研究凝集素或抗体微阵列等更快筛选方法的潜力。这是本研究第三阶段的目的，该阶段将侧重于确定可用作诊断和预后工具的最佳分析工具。

DESCRIPTION (provided by applicant): Rather than looking for specific cancer biomarkers (proteins or glycosylated proteins), we emphasize quantitative deglycosylation (removal of glycans) in unfractionated biological samples and displaying the removed glycans in quantitative glycan maps. Comparing glycomic profiles originating from healthy and diseased individuals should allow the assignment of structural changes associated with cancer. On the other hand, prognosis or a differential assessment of patients' health then relies on the isotopically-aided quantitative MS measurements of such glycan patterns. In the first two phases of our proposed research, clinically relevant samples will be screened through our well-established procedures while using the state-of- the-art MS-based methodologies and capillary electrophoresis. In Phase 1, the glycomic patterns of human blood serum collected from healthy females and males will be compared to those collected from ovarian, prostate, lung and colon cancer patients. Through bioinformatic and statistical evaluation a list of glycan markers that are associated with each type of cancer or with all types of cancer to be studied will be determined. This is necessary to establish quantitative trends in glycosylation or the occurrence of "glycosylation aberrations" and link these measurements to positively identified glycan structures. Glycomic profiles acquired for the same samples by CE-LIF will aid in determining changes that are due to changes in structural isomers which cannot be determined through MS. In Phase 2, the glycomic maps of human blood serum of cancer before and after treatment with a specific drug will be compared. In this phase, changes in the set of glycans defined in Phase 1 will be closely monitored and their changes as a result of cancer progression or remission will be evaluated. Phase 2 results will confirm or refute the potential glycan structures that will be defined as potential biomarkers in Phase 1. Upon the identification of these specific glycan changes or the set of glycan structures that change as a result of disease progression or remission, the potential of a faster screening approach such as lectin or antibody microarrays will be investigated. This is the aim of Phase 3 of this study which will focus on defining the best analytical tools that could be utilized as diagnostic and prognostic tool.