Urine Biomarker Discovery for Early Detection of Liver Cancer

用于早期检测肝癌的尿液生物标志物的发现

• 批准号: 7461209
• 负责人: Ying-Hsiu Su
• 金额: $ 38.19万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7461209
• 关键词: Biological; Biological Assay; Biological Markers; DNA; DNA Markers; DNA Modification Process; Detection; Development; Diagnosis; Disease; Early Diagnosis; Epigenetic Process; Genetic; Glycoproteins; Goals; Health; High Pressure Liquid Chromatography; Human; Individual; Institutes; Invasive; Knowledge; Liquid substance; Liver diseases; Malignant Neoplasms; Malignant neoplasm of liver; Methods; Modification; Monitor; Patients; Phase; Polysaccharides; Primary carcinoma of the liver cells; Public Health; Sampling; Screening for Hepatocellular Cancer; Sensitivity and Specificity; Site; Source; Staging; Structure; System; Technology; Time; Urinary tract; Urine; Viral; comparative; improved; macromolecule; outcome forecast; validation studies

DESCRIPTION (provided by applicant): Urine Biomarker Discovery for the Early Detection of Liver Cancer. Urine contains macro-molecules that can be used for the early detection of diseases and cancers that occur at non-urinary tract sites. Given the many advantages of using urine in biomarker monitoring, the goal of this project is to develop systems for the biomarker discovery of macromolecules (DNA and glycan) in urine that may ultimately improve the prognosis for such a disease. Comparative analysis of DNA modifications and glycan species (host and, where appropriate, viral) will be performed using urine samples from individuals at different stages of health and disease up to the diagnosis of liver cancer. This project will thus deliver new methods and new biomarkers for HCC and ultimately other cancers using urine as the biological fluid. These goals will be achieved by the following Aims. Aim 1: Detection of genetically or epigenetically modified DNA markers that have previously been associated with the development of HCC in urine as potential urine biomarkers for the early detection of HCC. The assays for detecting genetic and epigenetic modifications associated with HCC will be developed for analyzing urine DNA. The detection of each DNA marker in the urine of patients with different stages of liver disease and healthy subjects as the control will be performed to evaluate each marker as a candidate for a HCC, urine-derived biomarker panel. Aim 2: Determine if free glycan, isolated from human urine, can be used for biomarker discovery and the early detection of HCC. This Aim will determine if uncomplex glycans (presumably remnants of glycoproteins) present in urine can be a source for cancer biomarkers. The species of glycan, isolated from the urine of individuals, as a function of disease stage will be comparatively analyzed by HPLC. Glycan structures that appear to correlate with a diagnosis of liver disease will be characterized, and will be further explored as possible biomarkers. The promising urine-derived biomarkers obtained from Aim 1 and 2 will be used to propose another phase of study in which a larger scale, pre-validation study can be instituted to determine the sensitivity and specificity of each biomarker and the predicative value of a single biomarker or a combination of biomarkers for the early detection of HCC. This knowledge can ultimately be used so that a panel of multiple urine-derived biomarkers for the early detection of HCC can be constructed. Upon accomplishment of this project, we will have developed the technology platform for biomarker discovery that uses urine as the biological sample fluid, which can then be applied to other cancers. PUBLIC HEALTH RELEVANCE: This proposal aims to discover biomarkers for the early detection of liver cancer using urine as the biological sample fluid. The use of urine would be both appropriate and advantageous because urine can contain biomarkers from non- urinary tract sites, and the use of urine would be non-invasive. Upon accomplishment of this project, we will have developed the technology platform for biomarker discovery in urine, which can then be applied to other cancers.

描述（由申请人提供）：用于肝癌早期检测的尿液生物标志物发现。尿液中含有大分子，可用于早期检测发生在非尿路部位的疾病和癌症。鉴于在生物标志物监测中使用尿液的许多优点，该项目的目标是开发用于尿液中大分子（DNA和聚糖）的生物标志物发现的系统，最终可能改善此类疾病的预后。将使用来自不同健康和疾病阶段直至肝癌诊断的个体的尿液样本进行DNA修饰和聚糖种类（宿主和病毒（如适用））的比较分析。因此，该项目将为HCC提供新的方法和新的生物标志物，并最终使用尿液作为生物液体的其他癌症。这些目标将通过以下目标实现。目标1：检测先前与尿液中HCC发展相关的遗传或表观遗传修饰的DNA标记物，作为早期检测HCC的潜在尿液生物标志物。将开发用于检测与HCC相关的遗传和表观遗传修饰的检测方法，用于分析尿液DNA。将检测不同阶段肝脏疾病患者和健康受试者（作为对照）尿液中的每种DNA标记物，以评估每种标记物作为HCC、尿液衍生生物标志物组的候选物。目的2：确定从人尿液中分离的游离聚糖是否可用于生物标志物发现和HCC的早期检测。该目的将确定尿液中存在的非复合聚糖（推测为糖蛋白的残余物）是否可以作为癌症生物标志物的来源。将通过HPLC比较分析从个体尿液中分离的聚糖种类与疾病分期的关系。将表征似乎与肝病诊断相关的聚糖结构，并将进一步探索其作为可能的生物标志物。从目标1和2中获得的有希望的尿源性生物标志物将用于提出另一阶段的研究，其中可以建立更大规模的预验证研究，以确定每个生物标志物的灵敏度和特异性以及单个生物标志物或生物标志物组合用于早期检测HCC的预测价值。这些知识最终可以用于构建一组用于早期检测HCC的多种尿源性生物标志物。本项目完成后，我们将开发出以尿液为生物样品液的生物标志物发现技术平台，该技术平台可应用于其他癌症。 公共卫生相关性：该提案旨在使用尿液作为生物样本流体发现用于早期检测肝癌的生物标志物。使用尿液将是适当和有利的，因为尿液可以含有来自非泌尿道部位的生物标志物，并且尿液的使用将是非侵入性的。该项目完成后，我们将开发出尿液中生物标志物发现的技术平台，然后将其应用于其他癌症。