Pancreatic Cancer Detection Consortium

项目摘要/摘要 我们建议建立和利用一个独特的生物谱系资料库，专注于早期 通过收集独特和可靠的早期病变和血液样本来确定胰腺病变 来自有风险的患者和代表早期胰腺癌的病变的患者，匹配 来自同一患者的多组肿瘤和转移及对照组织，在许多情况下 纵向采集了同一病人的血液样本。我们将包括纵向获得的 样本来自有患胰腺癌风险的患者，这些患者后来会发展成胰腺癌， 包括囊性病变、慢性胰腺炎和成人糖尿病患者。这个独一无二的 资源将用于识别和表征在从 从癌前病变到原发肿瘤，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记物。这两种生物化石 候选生物标记物将可用于胰腺癌的合作研究 检测联盟。 具体1.我们将建立一个全面的组织收集(固定的，冷冻的和活的作为 有机物)表示发生的癌前病变、恶性病变和转移性病变的光谱 在尸检和手术中获得的个体患者中，并形成纵向的 从有胰腺癌风险的患者身上获取血液和组织样本 胰腺癌。 具体目的2.我们将评估15个新的胰腺癌进展的糖蛋白生物标记物 含有代表胰腺癌进展的细胞类型的人体组织样本 从早期癌前病变到原发癌和转移癌。 具体目的3.我们将评估15个新的胰腺糖蛋白生物标志物的表达 胰腺癌患者血清和血浆纵向标本中肿瘤进展的研究 癌症，并将这些与良性疾病患者的纵向样本进行比较。 特定目的4.应用噬菌体技术发现肿瘤细胞表面特异性抗原 显示人体胰腺类器官的方法。 具体目的5.评价和发现基于外切体的胰腺癌生物标记物 早期胰腺癌患者胞外液物蛋白质组无偏分析 病变(PanIN3和早期肿瘤)开发一组标记物，可以准确地预测 这些病变向胰腺癌的进展。

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.