Defining Secreted Glycan Alterations in Pancreatic Cancer

定义胰腺癌中分泌聚糖的改变

• 批准号: 7673935
• 负责人: Brian B. Haab
• 金额: $ 28.24万
• 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 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7673935
• 关键词: Adenocarcinoma; Affinity; Antibodies; Benign; Binding Proteins; Biological Markers; Blood Tests; CEACAM1; CEACAM5 gene; CEACAM7 gene; Cancer Control; Cancer Detection; Cancer Patient; Carbohydrates; Carcinoembryonic Antigen; Cell Adhesion Molecules; Cells; Data; Detection; Diagnostic; Discrimination; Disease; Early Diagnosis; Epithelial Cells; Frequencies; Glycoproteins; Incubated; Lead; Lectin; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Measurement; Measures; Methods; Microarray Analysis; Mucin-1 Staining Method; Mucins; Outcome; Pancreas; Pancreatic Diseases; Patients; Pattern; Phase; Polysaccharides; Protein Binding; Protein Microchips; Proteins; Proteomics; Public Health; Readiness; Research; Research Personnel; Sampling; Sensitivity and Specificity; Serum; Serum Proteins; Staging; Structure; Testing; base; cancer diagnosis; improved; insight; member; method development; novel; novel strategies; programs; research study

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地区分恶性疾病的方法的方法可以极大地改善胰腺癌患者的结局。众所周知，胰腺上皮细胞的恶性转化会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。糖基化的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，预计这些测试的细化可用于检测早期胰腺癌。我们的初步数据表明，一种新型的抗体微阵列技术允许在不同的蛋白质上有效检测聚糖，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的蛋白质，然后孵育聚糖结合蛋白（例如凝集素），以量化捕获的蛋白质上的特定聚糖。两类糖蛋白，粘蛋白和癌 - 凝血蛋白与抗原相关的蛋白质尤其与癌症相关，无论是在表达模式的改变和蛋白质上改变的聚糖结构中。在R21阶段，我们将确定这些蛋白质类别成员的多个特异性聚糖的水平，以检验以下假设：在特定蛋白质上测量特定癌症相关的聚糖，而不是仅测量蛋白质或仅仅测量糖素水平，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。使用粘液，CEA蛋白和R33期鉴定出的蛋白质的聚糖测量检测胰腺癌的敏感性和特异性将以来自胰腺癌，良性胰腺疾病，其他癌症和没有疾病的大量血清样品进行表征。我们期望表征这些测量值对疾病诊断的价值，并了解分泌蛋白质特定聚糖改变的一般性和频率。与公共卫生有关：在较早阶段更准确诊断癌症的能力可能会导致许多患者的结局改善。这项研究可能会导致检测癌症的血液测试，以及一个强大的，通常适用的平台，用于研究多种蛋白质的碳水化合物改变。