Biomarker validation for intraductal papillary mucinous neoplasms of the pancreas

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%。正因为如此，目前的胰腺癌筛查模式将继续失败，直到一种可治愈的胰腺癌被发现，或者直到更好的全身治疗方法被开发出来。胰腺导管内乳头状粘液瘤（IPMN）是一种囊性肿瘤，是唯一可在影像学上识别的胰腺癌前驱病变，在胰腺癌发展之前有机会进行干预。目前的实验室、内窥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。正因为如此，临床决策非常有争议，需要高风险疾病的标志物。这项多机构研究工作的目标是（具体目标#1）验证一组蛋白质标志物（MMP9, IL-4, sFASL, CA72.4），我们发现它们在识别高风险IPMN方面具有高度可靠性。最近的分析已经确定了两种单独的蛋白质标记模型（sFASL/IL-4和MMP9/CA72.4），它们本身对高危疾病的准确率（AUC）为86%。我们将在一组多机构的囊肿液样本（n=150）上验证这些标记

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%. Because of this, current screening paradigms for pancreatic cancer will continue to fail until a curable pancreatic cancer can be identified or until better systemic therapies can be developed. Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are cystic tumors that represent the only radiographically identifiable precursor lesion of pancreatic cancer and represent an opportunity for intervention prior to the development of pancreatic cancer. Current laboratory, endoscopic, and imaging technologies are unable to distinguish between IPMN that is at low-risk (low-grade dysplasia) or at high-risk (high-grade dysplasia) of becoming malignant. Because of this, clinical decision making is very controversial and markers of high-risk disease are needed. The goal of this multi-institutional research effort is to (specific aim #1) validate a group of protein marker (MMP9, IL-4, sFASL, CA72.4) that we have found to be highly reliable in identifying high- risk IPMN. Recent analyses have identified two separate models of protein markers (sFASL/IL-4 and MMP9/CA72.4) that by themselves had accuracy rates (AUC) of 86% for high-risk disease. We will validate these markers on a multi-institutional set of cyst fluid samples (n=150) utilizing antibody bead array. We will then incorporate these markers (specific aim #2) into a recently developed preoperative prediction model (nomogram) based on clinical and radiographic factors. This model will be developed from a multi- institutional dataset developed by the three participating institutions. This molecular-clinicopathologic nomogram will then be validated (specific aim #3) on a large group of patients enrolled into a prospective multi-institutional tria. The value of identifying markers of high-risk dysplasia in patients with IPMN cannot be overstated. Development of a preoperative test to accurately discriminate between low-risk and high-risk IPMN would allow patients with high-risk lesions to undergo resection prior to the development of an incurable disease, and enable patients with low-risk lesions to avoid operation and spare them the physical, emotional, and financial costs of pancreatectomy.