Urine Protein Biomarker Exploration in Ovarian Cancer

描述（由申请人提供）：大多数晚期卵巢癌患者生存率较低。努力用更有效的筛查方法来改善这一点显然是可取的。传统上，卵巢癌的筛查主要集中在影像学或血清标志物的使用上。然而，高昂的成像成本和20年来未能发现比CA125更好的生物标志物的研究表明，一种新的方法是值得的。因此，除了使用血清样本发现生物标志物外，我们将探索使用尿液作为替代体液的选择，以发现潜在的肽标志物，这可能最终转化为可靠的家庭筛查试验。这个试点项目将测试尿肽的假设，尿肽通常是小尺寸的，热力学稳定的，相互作用较少，可能是卵巢癌有用的尿标记物。在这个项目中，我们提出：1.)应用创新的蛋白质组学技术，如多维液相色谱（MD-LC），质谱，荧光标记与二维差分凝胶电泳（2D-DIGE），从卵巢癌分类亚型和年龄匹配的健康女性中生成尿肽谱。2)。利用生物信息学工具选择、鉴定和表征与卵巢癌特异性相关的新型尿肽，包括修饰。3)。开发可靠的尿液免疫测定和标准化方法，并在包括术前尿液标本和正常对照在内的大型研究中应用尿液标志物面板进行验证。这个项目如果成功，将从根本上改变卵巢癌的早期发现方法，并显著提高发现病例的存活率。

DESCRIPTION (provided by applicant): A majority of ovarian cancer patients presenting with diseases at late stages have poor survival rates. Efforts to improve this with more effective screening methods are clearly desirable. Traditionally, screening for ovarian cancer has focused on imaging or the use of serum markers. However, the high cost of imaging and the failure of 20 years of research to discover any better biomarkers than CA125, suggests a new approach would be worthwhile. Therefore, besides using serum samples for biomarker discovery, we will explore the option of using urine as an alternative body fluid to discover the potential peptide markers, which may ultimately be transformed into a reliable home screening test. This pilot project will test the hypothesis that urinary peptides, which normally are small size, thermodynamically stable and less interactive, could be useful urinary markers for ovarian cancer. In this project, we propose to: 1.) Apply innovative proteomic technologies such as multidimensional liquid chromatography (MD-LC), mass spectrometry, fluorescent labeling with two-dimensional differential gel electrophoresis (2D-DIGE) to generate urinary peptide profiles from the classified ovarian cancer subtypes and the age-matched healthy women. 2.) Using bio-informatic tools to select, identify and characterize the novel urinary peptides including modifications, which are specifically associated with ovarian cancers. 3.) Develop the reliable urine immunoassays and normalization methods, and apply the panel of urinary markers for validation in a large study including pre-operative urine specimens and normal controls. This project, if successful, could fundamentally shift the approach to the early detection of ovarian cancer and significantly improve the survival rate of cases detected.