Antibody bead array technology for diagnosis of pre-invasive pancreatic cancer

描述（由申请人提供）：成功进行癌症筛查的一个关键组成部分是确定一个病变，干预将导致延长生存期或治愈。IA期胰腺癌（最早可识别的病变，占所有胰腺癌的<<1%）切除患者的5年生存率约为35%。胰腺导管内乳头状粘液性肿瘤（IPMN）是胰腺癌的囊性肿瘤，是唯一可通过放射学检查识别的前驱病变，约占胰腺恶性肿瘤的20% - 30%。目前的实验室、内窥镜和成像技术无法区分IPMN是低风险（低度异型增生）还是高风险（高度异型增生）。我们最近发现了高风险IPMN患者的囊液中差异表达的蛋白质（IL-1b，IL-5，IL-8，MUC-2，MUC-4）。我们假设囊液的抗体珠阵列可用作诊断工具，以识别具有进展为恶性肿瘤的高风险的胰腺癌前囊肿（IPMN）的患者。在这个提议中，我们将把上面提到的差异表达的蛋白质整合到抗体珠阵列中，我们已经在囊液分析中使用该抗体珠阵列来区分良性胰腺囊肿。将对来自病理证实（切除）低风险（低和中度异型增生）和高风险（高度异型增生）IPMN患者的囊液进行抗体珠阵列分析。将比较低风险和高风险IPMN之间的差异蛋白表达，以评估发育不良的其他标志物。样本分类将用于开发预测高度异型增生的模型。该模型由手术获得的样本开发，然后将对内窥镜下获得的样本进行评价（内窥镜超声抽吸）。发展一种术前测试来区分低风险和高风险的IPMN将使高风险病变的患者在发展为基本上无法治愈的疾病之前被切除，并使低风险病变的患者避免手术，并使他们免于胰腺切除术的身体，情感和经济成本。 公共卫生相关性：胰腺导管内乳头状黏液性肿瘤（IPMN）是胰腺癌的影像学可识别的囊性前驱病变，从低度异型增生发展到高度异型增生再发展到癌。最近，我们已经从IPMN患者的囊液中鉴定出有希望的蛋白质生物标志物（MUC-2、MUC-4、IL-1b、IL-5、IL- 8），其在低风险和高风险病变中差异表达。在这项提案中，我们计划将这些生物标志物纳入我们先前在囊液分析中使用的抗体珠阵列中，并评估是否可以开发囊液测定来识别具有胰腺癌高风险的IPMN患者。

DESCRIPTION (provided by applicant): A critical component to successful cancer screening is the identification of a lesion for which intervention will result in prolonged survival or cure. The five-year survival of patients with resected stage IA pancreas cancer (the earliest identifiable lesion and <<1% of all pancreatic cancer) is approximately 35%. Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are cystic tumors that represent the only radiographically identifiable precursor lesion of pancreatic cancer and represent approximately 20% - 30% of pancreatic malignancy. Current laboratory, endoscopic, and imaging technologies are unable to distinguish between IPMN that is at low-risk (low-grade dysplasia) or high-risk (high-grade dysplasia) of becoming malignant. We have recently identified differentially expressed proteins (IL-1b, IL-5, IL-8, MUC-2, MUC-4) in the cyst fluid of patients with high-risk IPMN. We hypothesize that antibody bead array of cyst fluid can be utilized as a diagnostic tool to identify patients with pre-malignant cysts of the pancreas (IPMN) that are at high risk for progressing to malignancy. In this proposal we will incorporate the differentially expressed proteins noted above into an antibody bead array that we have used in cyst fluid analysis for the discrimination of benign pancreatic cysts. Antibody bead array analysis will be performed on cyst fluid from patients with pathologically proven (resected) low-risk (low and moderate grade dysplasia) and high-risk (high-grade dysplasia) IPMN. Differential protein expression will be compared between low-risk and high-risk IPMN to evaluate for additional markers of dysplasia. Sample classification will be used to develop a model for predicting high-grade dysplasia. This model, developed from operatively obtained samples, will then be evaluated on samples obtained endoscopically (endoscopic ultrasound aspiration). Development of a preoperative test to discriminate between low-risk and high-risk IPMN would allow patients with high-risk lesions to be resected prior to the development of an essentially incurable disease, and enable patients with low-risk lesions to avoid operation and spare them the physical, emotional, and financial costs of pancreatectomy. PUBLIC HEALTH RELEVANCE: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are radiographically identifiable cystic precursor lesions of pancreatic cancer that evolve from low-grade dysplasia to high-grade dysplasia to carcinoma. Recently we have identified promising protein biomarkers (MUC-2, MUC-4, IL-1b, IL-5, IL- 8) from the cyst fluid of patients with IPMN that are differentially expressed in low-risk and high-risk lesions. In this proposal we plan to incorporate these biomarkers into an antibody bead array that we have previously utilized in cyst fluid analysis and assess whether a cyst fluid assay can be developed to identify patients with IPMN who are at high-risk of developing pancreatic cancer.