Defining Secreted Glycan Alterations in Pancreatic Cancer

定义胰腺癌中分泌聚糖的改变

• 批准号: 7137150
• 负责人: Brian B. Haab
• 金额: $ 32.54万
• 依托单位: VAN ANDEL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7137150
• 关键词: antibody; clinical research; neoplasm /cancer; pancreas neoplasms; proteins

DESCRIPTION (provided by applicant): The development of methods to accurately detect early pancreatic cancer and to better differentiate benign from malignant disease could greatly improve the outcomes for pancreatic cancer patients. It is known that malignant transformation of epithelial cells of the pancreas results in alterations in the carbohydrate chains of certain proteins secreted or released by these cells. Glycosylated proteins form the basis for current biomarkers for detecting pancreatic cancer and other adenocarcinomas, and refinement of these tests are predicted to enable detection of early pancreatic cancer. Our preliminary data has shown that a novel antibody-microarray technology allows the efficient detection of glycans on distinct proteins and the identification of specific glycan structures associated with pancreatic cancer. The method uses antibody microarrays to capture specific proteins from serum samples, followed by the incubation of a glycan-binding protein (such as a lectin) to quantify specific glycans on the captured proteins. Two classes of glycoproteins, mucins and carcinoembryonic-antigen-related proteins, are particularly associated with cancer, both in altered expression patterns and in altered glycan structures on the proteins. In the R21 phase, we will determine the levels of multiple specific glycans on members of those protein classes to test the hypothesis that the measurement of specific cancer-associated glycans on specific proteins, as opposed to measuring just protein or just glycan levels, will yield improved sensitivities and specificities for cancer detection. The R33 phase of the project will expand and thoroughly test the approach. The sensitivity and specificity of detecting pancreatic cancer using measurements of glycans on mucins, CEA proteins, and proteins identified in the R33 phase will be characterized in a large set of serum samples from subjects with pancreatic cancer, benign pancreatic disease, other cancers, and no disease. We expect to characterize the value of these measurements for disease diagnostics and to gain insights into the generality and frequency of specific glycan alterations on secreted proteins. Relevance to public health: The ability to more accurately diagnose cancers at earlier stages could lead to improved outcomes for many patients. This research could lead to significantly improved blood tests for the detection of cancer, as well as a powerful, generally- applicable platform for studying carbohydrate alterations on multiple proteins.

描述（由申请人提供）：开发准确检测早期胰腺癌并更好区分良性和恶性疾病的方法可以极大地改善胰腺癌患者的治疗结果。已知胰腺上皮细胞的恶性转化导致这些细胞分泌或释放的某些蛋白质的碳水化合物链的改变。糖基化蛋白构成了当前检测胰腺癌和其他腺癌的生物标志物的基础，预计这些测试的改进将能够检测早期胰腺癌。我们的初步数据表明，一种新型抗体微阵列技术可以有效检测不同蛋白质上的聚糖，并鉴定与胰腺癌相关的特定聚糖结构。该方法使用抗体微阵列从血清样品中捕获特定蛋白质，然后孵育聚糖结合蛋白（例如凝集素）以量化捕获蛋白质上的特定聚糖。两类糖蛋白，粘蛋白和癌胚抗原相关蛋白，与癌症特别相关，无论是表达模式的改变还是蛋白质上聚糖结构的改变。在 R21 阶段，我们将测定这些蛋白质类别成员上的多个特定聚糖的水平，以测试以下假设：测量特定蛋白质上的特定癌症相关聚糖，而不是仅测量蛋白质或聚糖水平，将产生提高癌症检测的敏感性和特异性。该项目的 R33 阶段将扩展并彻底测试该方法。通过测量粘蛋白、CEA 蛋白和 R33 相中鉴定的蛋白上的聚糖来检测胰腺癌的敏感性和特异性将在来自胰腺癌、良性胰腺疾病、其他癌症和非胰腺癌受试者的大量血清样本中进行表征。疾病。我们期望表征这些测量对于疾病诊断的价值，并深入了解分泌蛋白上特定聚糖改变的普遍性和频率。与公共卫生的相关性：在早期阶段更准确地诊断癌症的能力可以改善许多患者的治疗结果。这项研究可能会显着改善癌症检测的血液检测，并为研究多种蛋白质的碳水化合物变化提供一个强大的、普遍适用的平台。

项目成果

Mucin glycosylation is altered by pro-inflammatory signaling in pancreatic-cancer cells.

胰腺癌细胞中的促炎信号传导会改变粘蛋白糖基化。

• 发表时间: 2009-04
• 影响因子: 4.4
• 作者: Wu, Yi;Nowack, D David;Omenn, Gilbert S;Haab, Brian B
• 通讯作者: Haab, Brian B

The prevalence and nature of glycan alterations on specific proteins in pancreatic cancer patients revealed using antibody-lectin sandwich arrays.

使用抗体-凝集素夹心阵列揭示了胰腺癌患者中特定蛋白质的聚糖改变的普遍性和性质。

• 发表时间: 2009-07
• 作者: Yue, Tingting;Goldstein, Irwin J;Hollingsworth, Michael A;Kaul, Karen;Brand, Randall E;Haab, Brian B
• 通讯作者: Haab, Brian B