Proteomic Biomarkers in Pancreatic Cyst Fluids

描述（由申请人提供）：胰腺癌是美国癌症死亡的第四大原因。大多数病例诊断晚，预后差。只有大约20%的少数患者接受手术切除治疗的目的将生存五年。有几种不同类型的独特的胰腺囊性肿瘤，有些具有恶性潜力。它们最初是良性病变，但产生粘蛋白的亚群可以通过一系列恶性转化而进展，导致腺癌的发展。手术切除是目前治疗粘液性囊性肿瘤的标准，但越来越多的胰腺囊肿被诊断放射学的改进所发现。在许多情况下，给定囊肿的病因及其恶性肿瘤的可能性仍然不确定，使得极难推荐或反对重大腹部手术干预（即，胰腺切除术）。使用细针抽吸的内窥镜超声来获得囊液以分析生物标志物和细胞学，但现有的生物标志物具有有限的灵敏度、特异性、预测值和准确性。 据我们所知，胰腺囊肿液的蛋白质组学分析尚未被描述。我们建议收集约20例患者的囊肿液进行蛋白质组学可行性研究。我们的假设是，每种囊肿类型的蛋白质组成都包含有用和独特的特征，可以通过对其蛋白质的详细映射来识别，并且这些独特的特征最终将帮助临床医生更好地管理胰腺囊性病变患者。具体目标1：通过二维凝胶蛋白质组学结合整体消化多维LC/MS/MS蛋白质组学方法表征各种囊肿类型液体的中分子量蛋白质。具体目标二：采用MALDI-TOF质谱和LC/MS/MS质谱技术分析不同类型包囊液中的小肽蛋白质组。预计该项目将提供各种类型胰腺囊性病变液体的详细蛋白质组学定义，从中可以选择新的和更有效的恶性肿瘤生物标志物并在未来进行验证。

DESCRIPTION (provided by applicant): Pancreatic cancer is the fourth leading cause of cancer death in the United States. The majority of cases are diagnosed late with poor prognosis. Only approximately 20% of the minority of patients that undergo surgical resection with curative intent will survive for five years. There are several different types of unique pancreatic cystic neoplasms and some have malignant potential. They are initially benign lesions, but a mucin-producing subgroup can progress through a series of malignant transformations, leading to the development of adenocarcinoma. Surgical resection is the current standard of care for mucinous cystic neoplasms, but a growing number of pancreatic cysts are being detected by improved diagnostic radiology. In many cases, the etiology of a given cyst and its potential for malignancy remains indeterminate, making it extremely difficult to make recommendations for, or against, a major abdominal surgical intervention (i.e., pancreatic resection). Endoscopic ultrasound with fine needle aspiration is used to obtain cyst fluid to analyze for biomarkers and cytology, but existing biomarkers have limited sensitivity, specificity, predictive values, and accuracy. To our knowledge, proteomic analysis of pancreatic cyst fluid has not been described. We propose to collect cyst fluids from approximately 20 patients to perform a proteomics feasibility study. Our hypothesis is that the protein composition of each individual cyst type contains useful and unique signatures that can be identified by detailed mapping of its proteins, and that these unique signatures will eventually help clinicians to better manage patients with cystic lesions of the pancreas. Specific Aim 1: To characterize the medium molecular weight proteins of the fluids of various cyst types by 2D gel proteomics complemented by a global digestion multidimensional LC/MS/MS proteomics approach. Specific Aim 2: To elicudate the small peptide proteome of the fluids of various cyst types using both MALDI-TOF mass spectrometry and LC/MS/MS mass spectrometry. It is anticipated that this project will provide detailed proteomic definition of the fluids of various types of cystic lesions of the pancreas from which new and more effective biomarkers of malignancy can be selected and validated in future.