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

描述（由申请人提供）：成功的癌症筛查的关键组成部分是确定干预将导致延长生存或治愈的病变。切除IA期胰腺癌（最早可识别病变，占所有胰腺癌的<<1%）患者的5年生存率约为35%。胰腺导管内乳头状粘液瘤（IPMN）是一种囊性肿瘤，是唯一影像学上可识别的胰腺癌前体病变，约占胰腺恶性肿瘤的20% - 30%。目前的实验室、内镜和成像技术无法区分IPMN是低风险（低级别发育不良）还是高风险（高级别发育不良）变为恶性。我们最近在高风险IPMN患者的囊肿液中发现了差异表达蛋白（IL-1b, IL-5, IL-8, MUC-2, MUC-4）。我们假设囊肿液抗体头阵列可以作为一种诊断工具，用于识别恶性前胰腺囊肿（IPMN）患者，这些患者有发展为恶性肿瘤的高风险。在本提案中，我们将把上述差异表达蛋白纳入抗体头阵列，我们已经在囊肿液分析中用于区分良性胰腺囊肿。抗体头阵列分析将对病理证实（切除）低风险（低和中度发育不良）和高风险（高度发育不良）IPMN患者的囊肿液进行分析。将比较低风险和高风险IPMN之间的差异蛋白表达，以评估不典型增生的其他标志物。样本分类将用于开发预测高度发育不良的模型。该模型由手术获得的样本开发，然后将在内窥镜（内窥镜超声抽吸）获得的样本上进行评估。开发一种区分低风险和高风险IPMN的术前测试，将使高风险病变的患者在发展为根本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，使他们免于胰腺切除术的身体、情感和经济成本。

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.