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

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变为恶性之前将其切除。通过高分辨率腹部成像可以早期发现部分胰腺癌前体——胰腺囊性肿瘤。腹部影像学应用的增加导致胰腺囊肿的诊断率提高，但目前尚无法准确确定哪些囊肿具有高恶性潜能，应予以切除。新的生物标志物可以帮助确定，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区分高恶性潜能胰腺囊肿和低恶性潜能胰腺囊肿的生物标志物。我们的总体假设是，特异性蛋白的表达和糖基化在高恶性潜能囊肿和低恶性潜能囊肿之间存在显著差异，这些分子构成了胰腺囊肿诊断的准确生物标志物。我们有一个全面的战略，生物标志物的发现，提炼和验证。多个临床站点将提供医学专业知识和高质量的样本集，生物标志物研究方面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。我们的技术策略是建立在新型糖蛋白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候选聚糖。通过对生物标记物异构体和糖型的反复表征和测试，将改进和提高最佳候选生物标记物的性能。关键的双盲验证研究将提供准确的生物标志物性能评估。该项目的成功将导致生物标志物在临床环境中得到验证；用于正在进行的edrn相关发现和验证研究的高质量样本集；以及对胰腺囊性肿瘤相关分子改变的进一步了解。

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.