Development of Chronic Pancreatitis Biomarkers

描述(申请人提供)：慢性胰腺炎，一种破坏性的胰腺疾病，很难诊断，并会出现各种症状。慢性胰腺炎的发病率尚不清楚；入院和出院总结显示，美国每年至少有6万名患者，但这些都是低估的，很明显，许多患者患有隐匿性疾病。胰腺炎给社会带来的经济负担是巨大的：由于失去工作和医疗保健费用，每年的负担接近25亿美元。目前还没有良好的血液检测来诊断慢性胰腺炎；标准是内窥镜检查和CT扫描 诊断方法以内窥镜超声(EUS)结合胰腺功能试验(PFT)最为敏感。我们提出了一个精心构建的算法，用于开发慢性胰腺炎的生物标记物。我们的候选生物标记物发现技术使用了最先进的蛋白质组学。我们团队有很好的合作经验，每个成员都被认为是各自应用领域的专家。初步数据显示，我们可以检测到胰腺炎背后的蛋白质，我们提供了原理上的证据，即在组织中发现的蛋白质可以通过酶联免疫吸附试验在血液中测量。我们已经招募了研究所需的三分之一以上的患者，这进一步支持了该建议的可行性，我们证明了iTRAQ蛋白质组技术是稳健和准确的，并且基于患者性别或种族血统的差异，胰腺炎蛋白质组中的异质性似乎不存在问题。我们的初步结果支持了我们的蛋白质发现理论，导致了一种可测量的胰腺炎生物标记物，并证明了该团队有效和成功工作的能力。将开发生物标记物的队列是高度定义的，并代表了使用生物标记物的临床环境。最初的生物标记物研究看起来很有希望。与目前用于慢性胰腺炎的内窥镜检查的黄金标准相比，准确的慢性胰腺炎生物标志物将具有巨大的临床益处，并可以节省时间和成本。

DESCRIPTION (provided by applicant): Chronic pancreatitis, a destructive disease of the pancreas, is difficult to diagnosis and can present with a variety of symptoms. The incidence of chronic pancreatitis is not known; hospital admission and discharge summaries suggest at least 60,000 patients in the US per year, however these are under-estimates and it is clear that many patients have occult disease. The financial burden of pancreatitis to society is substantial: with loss of work and health care costs, the burden approaches $2.5 billion annually. There are currently no good bloods tests for the diagnosis of chronic pancreatitis; endoscopic studies and CT scan are the standard approaches for the diagnosis, with endoscopic ultrasound (EUS) combined with pancreatic function tests (PFT) being the most sensitive. We propose a carefully constructed algorithm for the development of biomarkers for chronic pancreatitis. Our technology for candidate biomarkers discovery uses state-of-the- art proteomics. Our group has an excellent experience working together and each member is considered an expert in their applied field. The preliminary data reveals that we can detect the proteins that underlie pancreatitis and we provide proof of principle that the proteins discovered in tissue are measurable in the blood by ELISA. The feasibility of the proposal is further supported by the fact that we have recruited more than one third of the patients required for the study, we demonstrate that the ITRAQ proteomics techniques are robust and accurate, and that there appears to be no problem with heterogeneity in the pancreatitis proteome based on differences in the gender or ethnic origin of the patient. Our preliminary results support our thesis of protein discovery leading to a measurable biomarker for pancreatitis and also demonstrate the ability of the team to work effectively and successfully. The cohort in which the biomarkers will be developed are highly defined and represent the clinical setting in which the biomarker would be used. The initial biomarker studies look promising. An accurate biomarker for chronic pancreatitis would be of enormous clinical benefit and could save time and costs in comparison to the current gold standard of endoscopic testing for the disease.