Ultrasenstive vesicle analysis in precancerous pancreatic neoplasm (IPMN)

胰腺导管内乳头状粘液性肿瘤（IPMN），胰腺癌前病变的检测， 由于越来越多地使用高分辨率的横截面成像，这些囊性肿瘤 显示从低度异型增生发展到高度异型增生再到浸润性癌， 占所有胰腺癌的20-30%。某些形式的IPMN患者的管理仍然是 这是有争议的，因为目前的技术无法可靠地区分低风险和高风险的IPMN。 因此，有必要开发更好的工具，以促进有争议的病变的管理。目标 该提案的一个重要目的是开发和测试一种用于分析循环细胞外囊泡的超灵敏DEST方法 (EV)高风险的IPMN。具体而言，我们建议i）开发和验证与IPMN相关的新标记集 以前所未有的敏感性取得进展（目标1），以及ii）扩大和严格测试护理点方法 对前瞻性收集的临床样本进行分析（目标2）。我们假设高灵敏度的EV分析将 揭示了IPMN中生物标志物组成的有价值的信息，这是识别高风险病变的必要先决条件， 早期PDAC所提出的DEST方法有可能改变IPMN/早期PDAC癌症研究， 临床实践

The detection of intraductal papillary mucinous neoplasms (IPMN), precancerous lesions of the pancreas, is rising due to the increasing use of high-resolution cross-sectional imaging. These cystic neoplasms have been shown to evolve from low-grade dysplasia to high-grade dysplasia to invasive carcinoma and are believed to account for 20-30% of all pancreatic cancers. The management of patients with some forms of IPMN remains controversial because current technologies are unable to reliably distinguish between low and high risk IPMN. There is therefore a need to develop better tools to facilitate the management of controversial lesions. The goal of this proposal is to develop and test an ultra-sensitive DEST method for profiling circulating extracellular vesicles (EV) shed by high risk IPMN. Specifically, we propose to i) develop and validate new marker sets relevant for IPMN progression at unprecedented sensitivities (aim 1) and ii) expand and rigorously test the approach for point-of-care analyses in prospectively collected clinical samples (aim 2). We hypothesize that highly sensitive EV analysis will shed valuable light on biomarker composition in IPMN, a necessary prerequisite to identify high risk lesions and early PDAC. The proposed DEST method has the potential to transform IPMN/early PDAC cancer research and clinical practice.