Urine Protein Biomarker Exploration in Ovarian Cancer

卵巢癌尿蛋白生物标志物探索

• 批准号: 6966599
• 负责人: BIN YE
• 金额: $ 19.93万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6966599
• 关键词: bioinformatics; biomarker; clinical research; diagnosis quality /standard; early diagnosis; fluorescent dye /probe; liquid chromatography mass spectrometry; neoplasm /cancer diagnosis; ovary neoplasms; proteomics; surface enhanced laser desorption ionization; two dimensional gel electrophoresis; urinalysis; western blottings; women' s health

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.

描述（由申请人提供）：大多数晚期卵巢癌患者的生存率很低。用更有效的筛选方法来改善这一点的努力显然是可取的。传统上，卵巢癌的筛查集中在成像或血清标志物的使用上。然而，成像的高成本和20年的研究未能发现任何比CA 125更好的生物标志物，这表明新的方法是值得的。因此，除了使用血清样本进行生物标志物发现外，我们还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，最终可能转化为可靠的家庭筛查测试。这项试验项目将测试尿肽的假设，这通常是小尺寸，药物稳定性和较少的相互作用，可能是有用的尿标记物卵巢癌。在本项目中，我们建议：1.）应用创新的蛋白质组学技术，如多维液相色谱（MD-LC）、质谱、荧光标记与二维差异凝胶电泳（2D-DIGE），从分类的卵巢癌亚型和年龄匹配的健康女性中生成尿肽谱。2.）的情况。使用生物信息学工具来选择、鉴定和表征与卵巢癌特异性相关的新型尿肽（包括修饰）。3.）第三章建立可靠的尿液免疫分析和标准化方法，并将尿液标志物组应用于包括术前尿液标本和正常对照的大型研究。该项目如果成功，将从根本上改变卵巢癌的早期检测方法，并显著提高检测病例的存活率。