O-glycoproteins in the progression of liver disease

O-糖蛋白在肝病进展中的作用

• 批准号: 10450085
• 负责人: RADOSLAV GOLDMAN
• 金额: $ 50.5万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450085
• 关键词: Biological Assay; Biopsy; Cirrhosis; Complement; Detection; Development; Digestion; Disease; Disease Outcome; Disease Progression; Early Diagnosis; Enrollment; Etiology; Fibrosis; Galactosamine; Galactose; Glycopeptides; Glycoproteins; Goals; Hemopexin; Hepatitis C Antiviral; Hepatitis C virus; Liver; Liver Fibrosis; Liver diseases; Methods; Modification; Monitor; N-terminal; Neuraminic Acids; Neuraminidase; Participant; Pathology; Patient Recruitments; Patients; Peptides; Performance; Polysaccharides; Population; Primary carcinoma of the liver cells; Procedures; Proteins; Randomized Controlled Trials; Resistance; Sampling; Scheme; Serine; Serology; Serology test; Serum; Site; Structure; Technology; Therapeutic; Threonine; Time; University Hospitals; candidate marker; design; glycosylation; imaging modality; improved; liver development; new technology; non-invasive monitor; novel; patient population; rhomboid; virtual

Abstract We propose to apply targeted mass spectrometric methods to the analysis of specific O-glycoforms of proteins in the progression of liver disease to hepatocellular carcinoma (HCC). We have identified novel sialylated O- glycoform of liver secreted proteins significantly increased at progressive stages of liver disease. We propose to determine structure of the glycoforms and to evaluate extent of their presence on liver secreted glycoproteins. We will study association of the O-glycoforms with progressing stages of liver pathology by their direct quantification at specific sites of protein attachment in serum of patients. The O-glycoforms will be analyzed in combination with other markers identified in previous studies. We combine current concepts of disease mechanisms and advanced technologies to design improved serologic assays expected to complement biopsy and other non-invasive procedures in the assessment of liver disease. Non-invasive monitoring of liver disease progression to HCC is expected to influence optimal selection of therapeutic approaches and improve disease outcomes.

摘要 我们建议将靶向质谱学方法应用于蛋白质的特定O-糖型的分析 在肝病向肝细胞癌(肝细胞癌)的发展过程中。我们发现了一种新的唾液酸化O- 肝脏分泌蛋白的糖型在肝病进展期明显增加。我们建议 测定糖体的结构并评估其在肝脏分泌物中的存在程度 糖蛋白。我们将研究O-糖型与肝脏病理进展阶段的关系。 直接定量检测患者血清中蛋白附着的特定位点。O-糖型将会是 结合先前研究中确定的其他标记进行分析。我们结合了当前的概念 疾病机制和先进技术，以设计改进的血清学检测方法，有望 补体活检和其他非侵入性检查在肝病评估中的应用。非侵入性 肝病进展到肝细胞癌的监测有望影响最佳治疗选择 方法和改善疾病结果。