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

抗体珠阵列技术诊断浸润前胰腺癌

• 批准号: 8191333
• 负责人: Peter J Allen
• 金额: $ 19.59万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-18 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8191333
• 关键词: Accounting; Antibodies; Benign; Biological Assay; Biological Markers; Blinded; Carcinoma; Classification; Clinical; Cyst Fluid; Cystic Lesion; Cystic Neoplasm; Data; Development; Diagnosis; Diagnostic; Discrimination; Disease; Dysplasia; Early Diagnosis; Emotional; Excision; Financial cost; IL8 gene; Imaging technology; Interleukin-5; Intervention; Laboratories; Lesion; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Measurement; Modeling; Morbidity - disease rate; Mucinous Neoplasm; Mucins; Pancreas; Pancreatectomy; Pancreatic Cyst; Papillary; Pathologic; Patients; Premalignant; Proteins; Publishing; Reporting; Research; Resected; Risk; Sampling; Screening for cancer; Serous; Specimen; Staging; Systemic Therapy; Technology; Testing; Ultrasonography; Validation; clinically relevant; cost; cytokine; high risk; improved; mortality; operation; protein expression; tool

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.

描述（由申请人提供）：成功癌症筛查的关键成分是鉴定干预措施会导致长时间生存或治愈的病变。切除的IA胰腺癌患者的五年生存期（最早可识别的病变和所有胰腺癌的1％）约为35％。胰腺的导管内乳头状肿瘤（IPMN）是囊性肿瘤，代表胰腺癌的唯一可识别的X射线照片前体病变，约占胰腺恶性肿瘤的20％-30％。当前的实验室，内窥镜和成像技术无法区分低风险（低级发育异常）或高风险（高级发育异常）的IPMN。我们最近在具有高危IPMN的患者的囊肿液中鉴定了差异表达的蛋白（IL-1B，IL-5，IL-8，MUC-2，MUC-4）。我们假设可以将囊肿液的抗体珠阵列用作诊断工具，以识别胰腺前恶性囊肿（IPMN）的患者，这些患者面临着高风险到恶性肿瘤的高风险。在此提案中，我们将将上述差异表达的蛋白质纳入抗体珠阵列中，我们在囊肿流体分析中用于区分良性胰腺囊肿。抗体珠阵列分析将对患有病理证明（切除的）低风险（低风险和中等级发育不良）和高危（高级发育异常）IPMN的患者进行囊肿液。将比较低风险和高危IPMN之间的差异蛋白表达，以评估其他发育不良标记。样本分类将用于开发用于预测高级发育不良的模型。然后将根据内窥镜获得的样品（内窥镜超声抽吸）评估该模型。开发术前测试以区分低风险和高风险IPMN，将使患有高风险病变的患者在开发基本无法治愈的疾病之前切除，并使低风险病变的患者避免手术并避免其身体，情感，情感上的胰腺切除术的经济成本和财务成本。 公共卫生相关性：胰腺的导管内粘液性肿瘤（IPMN）是胰腺癌的X射线照相式囊性前体病变，可从低度发育异常到高级发育不良发展为癌症。最近，我们从IPMN患者的囊肿中鉴定了有希望的蛋白质生物标志物（MUC-2，MUC-4，IL-1B，IL-5，IL-8），这些囊肿在低危和高风险病变中差异表达。在此提案中，我们计划将这些生物标志物纳入我们以前在囊肿液分析中使用的抗体珠阵列，并评估是否可以开发囊肿液分析以识别患有高风险胰腺癌高风险的IPMN患者。