Early detection of pancreatic cancer in diabetics

描述(申请人提供)：胰腺癌是一种很难诊断的高致命性疾病。该病死亡率高的主要原因是确诊时疾病已进入晚期，缺乏有效的治疗方法。由于胰腺癌的发病率很低(0.01%)，在筛查高危人群，如新发的2型糖尿病患者方面，早期发现将是最具成本效益的。临床和研究已经证实了胰腺癌和新发的2型糖尿病之间的联系。开发一种高精度的基于血液的检测方法来检测这一人群中的胰腺癌，将代表着胰腺癌早期检测的突破。如果在这一高危人群中每年进行这样的血液测试，可能会成为一种有效且廉价的初步靶向筛查方法。在这个项目中，我们建议开发和表征一种基于血液的蛋白质组学特征，使胰腺癌患者能够早期发现新发的糖尿病患者。具体目标如下：特定目标1：利用定量蛋白质组学在全球范围内无偏见地发现糖尿病患者血液中与胰腺癌相关的差异蛋白质；特定目标2：针对35个选定的生物标记物候选建立靶向蛋白质组分析；特定目标3：建立用于检测糖尿病患者早期胰腺癌的蛋白质组学标志物(生物标志物小组)；特定目标4：评价蛋白质组学标志物在无症状患者检测胰腺癌中的作用。这项建议建立在我们对胰腺肿瘤发生的长达十年的系统研究、胰腺癌生物标记物开发方面先前发现的丰富资源、来自不同机构的具有良好特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，以促进糖尿病患者早期发现胰腺癌，将缓解目前高危人群的长期工作，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.