Detection of Pre-Invasive Pancreatic Cysts Using Protein and Glycan Biomarkers

使用蛋白质和聚糖生物标志物检测侵袭前胰腺囊肿

• 批准号: 7982742
• 负责人: Peter J Allen
• 金额: $ 73.24万
• 依托单位: VAN ANDEL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-17 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7982742
• 关键词: Abdomen; Address; Affinity Chromatography; Antibodies; Area; Biological Markers; Blood; Blood specimen; Cancer Detection; Clinical; Cyst; Cyst Fluid; Cystic Neoplasm; Detection; Development; Diagnosis; Double-Blind Method; Early Detection Research Network; Early Diagnosis; Excision; Experimental Designs; Goals; Image; Immunohistochemistry; Invasive Lesion; Lead; Lectin; Malignant - descriptor; Malignant neoplasm of pancreas; Measurement; Measures; Medical; Methods; Molecular; Mucins; Outcome; Pancreas; Pancreatic Cyst; Patients; Performance; Polysaccharides; Premalignant; Principal Investigator; Protein Isoforms; Proteins; Research; Resolution; Sampling; Site; Suspension substance; Suspensions; Technology; Testing; Validation; Variant; cancer care; cell type; clinical research site; experience; glycosylation; improved; novel; research study; success; validation studies

DESCRIPTION (provided by applicant): The current best hope for the successful treatment of pancreatic cancer is the removal of pre-invasive lesions before they become malignant. The early detection of a portion of pancreatic cancer precursors- cystic neoplasms of the pancreas-is possible through high-resolution abdominal imaging. The increased use of abdominal imaging has led to a higher rate of identifying pancreatic cysts, but currently it is not possible to accurately determine which cysts have high malignant potential and should be removed. New biomarkers that could assist that determination would lead to more successful outcomes for patients with pancreatic cysts. Therefore, the goal of this research is to develop biomarkers for distinguishing pancreatic cysts with high malignant potential from those with low malignant potential. Our overall hypothesis is that the expression and glycosylation of specific proteins are significantly different between cysts with high malignant potential and cysts with low malignant potential, and that these molecules form accurate biomarkers for the diagnosis of pancreatic cysts. We have a comprehensive strategy for biomarker discovery, refinement, and validation. Multiple clinical sites will contribute the medical expertise and the high-quality sample sets, and experienced statistical expertise in biomarker research will guide the experimental design for biomarker discovery, pre-validation, and validation. Our technological strategy is built on the powerful combination of novel glycoproteomics biomarker discovery methods and complementary antibody array methods for the high-throughput and precise profiling of multiple protein and glycan candidates. Through the iterative characterization and testing of biomarker isoforms and glycoforms, the performance of the best candidate biomarkers will be refined and improved. Pivotal double-blind validation studies will provide accurate assessments of biomarker performance. The success of this project will result in biomarkers to be validated in clinical settings; high-quality sample sets to be used in ongoing EDRN-associated discovery and validation studies; and an improved understanding of the molecular alterations associated with pancreatic cystic neoplasms.

描述（由申请人提供）：目前成功治疗胰腺癌的最大希望是在浸润前病变恶化之前切除它们。通过高分辨率腹部成像，可以早期发现胰腺癌的一部分前体-胰腺囊性肿瘤。腹部成像的使用增加导致胰腺囊肿的识别率更高，但目前无法准确确定哪些囊肿具有高恶性潜力并应予以切除。新的生物标志物可以帮助确定这一点，这将为胰腺囊肿患者带来更成功的结果。因此，本研究的目的是开发生物标志物，用于区分具有高恶性潜能的胰腺囊肿和具有低恶性潜能的胰腺囊肿。我们的总体假设是，特异性蛋白质的表达和糖基化在具有高恶性潜能的囊肿和具有低恶性潜能的囊肿之间是显著不同的，并且这些分子形成用于诊断胰腺囊肿的准确生物标志物。我们有一个全面的生物标志物发现，提炼和验证的战略。多个临床研究中心将提供医学专业知识和高质量的样本集，生物标志物研究中经验丰富的统计专业知识将指导生物标志物发现，预验证和验证的实验设计。我们的技术策略建立在新型糖蛋白质组学生物标志物发现方法和互补抗体阵列方法的强大组合之上，用于高通量和精确分析多种蛋白质和聚糖候选物。通过生物标志物同种型和糖型的迭代表征和测试，最佳候选生物标志物的性能将得到改进和提高。首次双盲验证研究将提供生物标志物性能的准确评估。该项目的成功将导致生物标志物在临床环境中得到验证;高质量的样本集将用于正在进行的EDRN相关发现和验证研究;以及对胰腺囊性肿瘤相关分子改变的更好理解。