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方法应用于蛋白质特定O-糖型的分析 肝脏疾病进展为肝细胞癌（HCC）。我们已经确定了新的唾液酸化O- 肝脏分泌蛋白的糖型在肝脏疾病的进展阶段显著增加。我们提出 确定糖型的结构并评价其在肝脏分泌的 糖蛋白我们将研究O-糖型与肝脏病理学进展阶段的关系， 在患者血清中蛋白质附着的特定位点直接定量。O-糖型将是 与先前研究中鉴定的其他标志物组合分析。我们将联合收割机的现有概念 疾病机制和先进的技术来设计改进的血清学检测， 补体活组织检查和其他非侵入性程序在肝脏疾病的评估。无创 监测肝病进展为HCC预计将影响治疗方案的最佳选择。 方法和改善疾病的结果。