Pancreatic Cancer Detection Consortium

项目总结/摘要 我们建议建立和利用一个独特的生物标本库， 通过收集独特而强大的早期病变和血液样本， 来自风险患者和具有代表胰腺癌早期病变的患者， 来自相同患者的肿瘤和转移组织以及对照组织，并且在许多情况下， 从相同的患者纵向获得血液样本。我们将包括纵向获得的 来自有患胰腺癌风险的患者的样品，这些患者继续发展为胰腺癌， 包括患有囊性病变、慢性胰腺炎和成人发病糖尿病的患者。这种独特 资源将用于识别和表征在从 从癌前病变到原发性肿瘤，并评估这些患者的血液样本， 在疾病进展的早期和晚期都存在生物标志物。两个生物样本 和候选生物标志物将可用于胰腺癌内的合作研究 侦测联盟 具体1.我们将建立一个全面的组织收集（固定，冷冻和活体， 类器官），代表发生的癌前病变到恶性病变和转移性病变的范围 在尸检和手术中获得的个体患者中，并纵向收集 从有胰腺癌风险的患者中获得血液和组织样本， 胰腺癌 具体目标2。我们将评估胰腺癌进展的15种新的糖蛋白生物标志物， 含有代表胰腺癌进展的细胞类型的人组织样品， 早期癌前病变到原发性和转移性癌症。 具体目标3。我们将评估15种新的胰腺癌糖蛋白生物标志物的表达， 在发生胰腺癌的患者的纵向样品血清和血浆中的癌症进展 癌症，并将这些与良性疾病的适当患者的纵向样本进行比较。 具体目标4。发现细胞表面抗原特异性恶性状态通过应用噬菌体- 展示人类胰腺类器官的方法。 具体目标5.通过使用外泌体来评估和发现胰腺癌的生物标志物， 来自早期胰腺癌患者的外泌体货物的无偏蛋白质组学分析 病变（PanIN 3和早期肿瘤），以开发一组标记物，可以准确预测 这些病变进展为胰腺癌。

Project Summary/Abstract We propose to build and utilize a unique repository of biospecimens that are focused on early pancreatic lesions by assembling a unique and robust collection of early lesions and blood samples from patients at risk and those with lesions representing early stages of pancreatic cancer, matched sets of tumors and metastasis and control tissues from the same patients, and in many cases longitudinally obtained blood samples from the same patients. We will include longitudinally obtained samples from patients at risk for developing pancreatic cancer that go on to develop pancreatic cancer, including patients with cystic lesions, chronic pancreatitis, and adult onset diabetes. This unique resource will be used to identify and characterize biomarkers that develop during the progression from premalignant lesions to primary tumors, and to evaluate blood samples from these patients for the presence of biomarkers at both early and late stages of disease progression. Both the biospecimens and candidate biomarkers will be available for collaborative studies within the Pancreatic Cancer Detection Consortium. Specific 1. We will establish a comprehensive collection of tissues (fixed, frozen and living as organoids) representing the spectrum of premalignant to malignant and metastatic lesions that occur within individual patients obtained at autopsy and at surgery, and develop a collection of longitudinally obtained blood and tissue specimens from patients at risk for pancreatic cancer and that develop pancreatic cancer. Specific Aim 2. We will evaluate 15 novel glycoprotein biomarkers of pancreatic cancer progression in human tissue samples containing cell types that represent the progression of pancreatic cancer from early premalignant lesions to primary and metastatic cancer. Specific Aim 3. We will evaluate the expression of 15 novel glycoprotein biomarkers of pancreatic cancer progression in longitudinal samples serum and plasma of patients that develop pancreatic cancer, and compare these to longitudinal samples of appropriate patients with benign diseases. Specific Aim 4. Discover cell surface antigens specific to the malignant state by applying phage- display approaches to human pancreatic organoids. Specific Aim 5. To evaluate and discover exosome-based biomarkers of pancreatic cancer by using an unbiased proteomic analysis of exosomal cargo derived from patients with early stage pancreatic lesions (PanIN3 eand early stage tumors) to develop a panel of markers that can accurately predict the progression of these lesions towards pancreatic cancer.