Early detection of pancreatic cancer in diabetics

描述（由申请人提供）：胰腺癌是一种非常难以诊断的高致死率疾病。这种疾病的高死亡率主要是由于在诊断时疾病的晚期和缺乏有效的治疗。由于胰腺癌的患病率较低（0.01%），早期检测对于筛查高危人群（如新发2型糖尿病患者）是最具成本效益的。临床和研究已经证实了胰腺癌和新发2型糖尿病之间的联系。开发一种高度精确的基于血液的检测方法来检测这一人群的胰腺癌，将是胰腺癌早期检测的一个突破。如果在这一高危人群中每年进行一次这样的血液检查，可以作为一种有效而廉价的初步针对性筛查方法。在这个项目中，我们提出开发和表征一种基于血液的蛋白质组学特征，可以早期检测胰腺癌患者的新发糖尿病。具体目标如下：具体目标1：使用定量蛋白质组学在糖尿病患者血液中公正地发现与胰腺癌相关的差异蛋白；具体目标2：开发35个选定的候选生物标志物的靶向蛋白质组学分析；特异性目标3：建立检测糖尿病患者早期胰腺癌的蛋白质组学特征（生物标志物面板）；特异性目的4：评估蛋白质组学特征在无症状患者胰腺癌检测中的作用。该提案建立在我们长达十年的胰腺肿瘤发生系统研究，胰腺癌生物标志物开发的丰富资源，来自不同机构的良好表征的研究队列，以及我们开发和实施的尖端蛋白质组学平台技术的基础上。成功开发一种基于血液的检测方法，以促进糖尿病患者胰腺癌的早期检测，将缓解目前高风险人群的长期检查，并为治疗早期癌症提供至关重要的拦截机会。

DESCRIPTION (provided by applicant): Pancreatic cancer is a highly lethal disease that is very difficult to diagnose. The high mortality of this disease is predominantly due to the advanced stage of disease at the time of diagnosis and a lack of effective treatments. Due to the low prevalence of pancreatic cancer (0.01%), early detection would be most cost-effective in screening increased-risk populations, such as new-onset type-2 diabetics. Clinical and research studies have substantiated the link between pancreatic cancer and new-onset type-2 diabetes. Development of a highly accurate blood-based test to detect pancreatic cancer in this population would represent a breakthrough in early detection of pancreatic cancer. Such a blood test, if used on an annual basis in this higher-risk population, could serve as an effective and inexpensive method for initial targeted screening. In this project, we proposed to develop and characterize a blood-based proteomics signature that allows early detection of pancreatic cancer patients with new-onset diabetics. The Specific Aims are as follows: Specific Aim 1: unbiased global discovery of differential proteins associated with pancreatic cancer in the blood of diabetic patients using quantitative proteomics; Specific Aim 2: development of targeted proteomics assay for 35 selected biomarker candidates; Specific Aim 3: establishment of a proteomics signature (biomarker panel) for detecting early stage pancreatic cancer in diabetic patients; Specific Aim 4: evaluation of the proteomics signature in detecting pancreatic cancer in asymptomatic patients. This proposal builds on our decade-long systematic study of pancreatic tumorigenesis, the rich resource of previous discoveries in pancreatic cancer biomarker development, well-characterized study cohorts from different institutions, as well as cutting-edge proteomics platform technologies that we have developed and implemented. Successful development of a blood-based assay to facilitate the early detection of pancreatic cancer for diabetic patients would alleviate the current prolonged work-up of higher-risk populations and provide critically important interception opportunities to treat earlier stage cancer.