Targeted Glycomics and Affinity Reagents for Cancer Biomarker Development

用于癌症生物标志物开发的靶向糖组学和亲和试剂

• 批准号: 8698717
• 负责人: Brian B. Haab
• 金额: $ 42.64万
• 依托单位: VAN ANDEL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-08 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698717
• 关键词: Address; Affinity; Antibodies; Antigens; Area; Benign; Binding; Biochemical; Bioinformatics; Biological; Biological Assay; Biological Markers; Biology; Blinded; CA-19-9 Antigen; Cancer Detection; Cancer Patient; Cancer Prognosis; Carcinoembryonic Antigen; Caring; Clinical; Computer software; Data; Detection; Development; Diagnosis; Diagnostic Procedure; Differential Diagnosis; Gene Expression; Genetic; Glycobiology; Goals; Individual; Lead; Lectin; Lesion; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Mass Spectrum Analysis; Measurement; Methods; Molecular Profiling; Monitor; Pancreas; Pancreatic Diseases; Patient Care; Patients; Pattern; Performance; Polysaccharides; Reagent; Research; Resources; Sampling; Sensitivity and Specificity; Serum; Shotguns; Specificity; Staging; Structure; Subgroup; Testing; Time; Tn antigen; Training; Variant; Work; base; clinically relevant; glycosylation; high risk; improved; new technology; novel; novel diagnostics; overexpression; performance tests; research study; screening; success; tool; tumor

DESCRIPTION (provided by applicant): New biomarkers for pancreatic cancer are urgently needed on several fronts: screening among high-risk individuals, accurate diagnosis of suspected cancer, prognosis and treatment prediction, and monitoring the progress of tumors during the course of treatment. The CA 19-9 antigen is the best current marker for pancreatic cancer, yet its use is limited owing to its lack of expression in a significant fraction of patient. The goal of this research is to develop a panel of biomarkers for pancreatic cancer that specifically identifies patients that are either high or low in CA 19-9 and that would perform well enough to impact patient care. Research has shown that the lack of CA 19-9 elevation in certain patients is due to genetic or expression alterations in the glycosylation machinery not found in CA19-9-expressing patients. In addition, we have shown that certain patients who are low in CA 19-9 produce alternative glycans that can be used to specifically identify them. Our hypotheses are 1) the CA 19-9-low and CA 19-9-high tumors are distinct biological entities that produce divergent glycan structures; and 2) the detection of the glycans specific to CA 19-9-low tumors used in combination with the detection of CA 19-9 forms a highly accurate biomarker panel. We will use powerful glycomics tools guided by new biological/biochemical information to test these hypotheses. In Aim 1, we will use the development of new affinity reagents combined with Shotgun Glycomics to identify and characterize glycans that may specifically detect CA 19-9-low tumors. In Aim 2, we will derive biological information from gene expression analysis to further guide the testing of glycans for differential expression. In Aim 3, the identified affinity reagent will be used in the testing and development of biomarker panels. The completion of these aims will result in new biomarkers to improve the care of pancreatic cancer patients, the advancement of a new strategy for identifying and developing glycan-based biomarkers, and new resources for other glycobiology projects.

描述（由申请人提供）：急需多个方面需要胰腺癌的新生物标志物：在高危个体之间进行筛查，准确诊断可疑癌症，预后和治疗预测，并监测治疗过程中肿瘤的进展。 CA 19-9抗原是胰腺癌的最佳当前标志物，但由于其在很大一部分患者中的表达不足，因此其使用量限制。这项研究的目的是为胰腺癌开发一个生物标志物，该小组专门鉴定出CA 19-9中高或低的患者，并且表现良好 足以影响患者护理。研究表明，某些患者缺乏CA 19-9升高是由于表达CA19-9的患者未发现糖基化机制的遗传或表达改变。此外，我们已经表明，在CA 19-9中较低的某些患者会产生可用于专门识别它们的替代聚糖。我们的假设是1）CA 19-9-高和CA 19-9高肿瘤是产生不同聚糖结构的不同生物学实体； 2）检测特定于Ca 19-9-高肿瘤与CA 19-9结合使用的聚糖形成了一个高度精确的生物标志物面板。我们将使用以新的生物学/生化信息为指导的强大糖化工具来检验这些假设。在AIM 1中，我们将使用新的亲和力试剂与shot弹枪糖基质的开发来识别和表征可能专门检测Ca 19-9-低肿瘤的聚糖。在AIM 2中，我们将从基因表达分析中得出生物学信息，以进一步指导聚糖测试以差异表达。在AIM 3中，确定的亲和力试剂将用于生物标志物面板的测试和开发。这些目的的完成将导致新的生物标志物改善胰腺癌患者的护理，鉴定和开发基于聚糖的生物标志物的新战略的发展以及其他糖生物学项目的新资源。