Pancreatic Cancer Detection Consortium

摘要 这项在胰腺癌检测联盟中继续进行的提案将进一步建立和加强我们的 生物样本资源，收集有胰腺癌风险的患者的纵向血液样本 和独特的组织资源，包括罕见的胰腺癌前病变。我们建议继续， 加强我们对基于血液和基于成像的生物标志物的发现和验证，这些生物标志物有可能 检测和区分可能进展为癌症的胰腺病变的最早可能阶段。 这一提议源于3.5年前发起的一项持续努力， 约469例已知生殖系突变或具有未知病因的显著遗传风险的患者 (more超过2例受影响，无明确的突变）。我们前瞻性地收集生物 样本（100 mL血液）和详细的临床数据，每6个月从代表 具有检测胰腺癌潜力生物标志物临床应用的目标人群。在 除了有遗传风险的患者外，我们将继续收集以下患者组的纵向样本： 胰腺癌风险增加：胰腺囊性肿瘤或慢性胰腺炎患者，以及新 发病糖尿病（NOD）。我们还提出了三个生物标志物研究的具体目标，这些目标已经发展出来 在上一个奖项中。一个目标将建立在我们先前的粘蛋白类型生物标志物的结果基础上， 通过检查一组额外生物标志物改善癌症检测的潜力来研究相关糖蛋白 在疾病进展的最早阶段的临床诊断之前。第二个目标将考察 新鉴定的CEACAM6抗体，通过免疫组织化学鉴定胰腺中的最早病变 和最先进的成像模式。第三个目标将决定一个小组的性能特点， 基于外泌体的生物标志物检测早期胰腺癌并将良性囊性病变与 那些发展成癌症的人

Abstract This proposal to continue in the Pancreatic Cancer Detection Consortium will further build and enhance our biospecimen resource that collects longitudinal blood samples on patients at risk of developing pancreatic cancer and unique tissue resources that include rare pancreatic premalignant lesions. We propose to continue and enhance our discovery and validation of blood-based and imaging-based biomarkers that have the potential to detect and differentiate the earliest possible stages of pancreatic lesions that are likely to progress to cancer. This proposal proceeds from an ongoing effort that was initiated 3.5 years ago in which we have enrolled approximately 469 patients with known germline mutations or with significant inherited risk of unknown etiology (more than 2 affected with no defined mutations) for pancreatic cancer. We prospectively collect biological specimens (100 mL blood) and detailed clinical data every six months from an at-risk cohort that represents the target population envisioned for clinical application of biomarkers with potential to detect pancreatic cancer. In addition to patients with inherited risk, we will continue to collect longitudinal samples on groups of patients with increased risk of pancreatic cancer: those with pancreatic cystic neoplasms or chronic pancreatitis, and new onset diabetes (NOD). We also propose three biomarker research specific aims that have grown out of progress during the previous grant award. One aim will build upon our previous results with mucin type biomarkers and related glycoproteins by examining the potential of a set of additional biomarkers to improve detection cancer prior to clinical diagnosis in the earliest stages of disease progression. A second aim will examine the capacity of newly identified antibodies to CEACAM6 to identify earliest lesions in the pancreas by immunohistochemistry and state of the art imaging modalities. A third aim will determine the performance characteristics of a panel of exosome-based biomarkers detecting early pancreatic cancer and differentiating benign cystic lesions from those that progress to cancer.