Development of the GlycoHCCTyper for the early detection of HCC

开发用于早期检测 HCC 的 GlycoHCCTyper

• 批准号: 10382624
• 负责人: Stephen Castellino
• 金额: $ 42.84万
• 依托单位: GLYCOPATH, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10382624
• 关键词: AFP gene; Acute Disease; Address; Algorithms; Antibodies; Biological Assay; Biological Markers; Blinded; Blood specimen; CA-125 Antigen; Ceruloplasmin; Chronic Disease; Cirrhosis; Clinical; Detection; Development; Diagnosis; Early Diagnosis; Ensure; Evaluation; FDA approved; Glycoproteins; Goals; Hand; Haptoglobins; Hemopexin; Image; Immunoglobulin G; Laboratories; Lectin; Link; Low-Molecular-Weight Kininogen; MALDI-TOF Mass Spectrometry; Malignant neoplasm of liver; Mass Spectrum Analysis; Medical; Methods; Modification; Orosomucoid; Patients; Phase; Polysaccharides; Primary Malignant Neoplasm of Liver; Primary carcinoma of the liver cells; Process; Proteins; Proteomics; Reproducibility; Sampling; Serum; Slide; Small Business Technology Transfer Research; South Carolina; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; System; Technology; Time; Tissue Sample; Transferrin; Universities; Validation; Vitamin D-Binding Protein; Work; alpha 2-Glucoproteins; alpha-Fetoproteins; apolipoprotein D; biomarker signature; cancer biomarkers; clinical development; cohort; design; glycoproteomics; glycosylation; histidine-rich glycoprotein; instrument; mass spectrometer; non-alcoholic fatty liver disease; nonalcoholic steatohepatitis; novel; prospective; protein purification; sample collection; sugar

Alterations in glycosylation have long been associated with the development and progression of many types of chronic and acute diseases. Our group (Mehta) was one of the first to perform glycan analysis in serum and perform proteomics on specific glycoforms (glycoproteomics). Using such methods, we identified a number of serum glycoproteins with altered glycosylation in hepatocellular carcinoma, a primary cancer of the liver. However, because of limitations in technology, we were forced to either examine each protein one at a time or examine pools of proteins without the ability to link a particular glycan to a given protein. In some situations, we performed structural glycan analysis on purified proteins which provided the best “biomarker” information, but took days to weeks for analysis. Alternatively, we could forgo true structural information and use lectins to determine if only one specific sugar moiety was present, and perform analysis in a more rapid manner. But again, this was generally done only on one protein at a time. In all of these situations, the biomarker potential of these glycoproteins was diminished because of the technology used. To address this limitation, GlycoPath has recently developed a streamlined antibody capture slide array approach to directly profile N-linked glycans on captured serum glycoproteins. This process requires only a few microliters of sample and utilizes simple methods that require no protein purification or sugar modifications prior to analysis. This method is referred to as the GlycoTyper. In this method, N-linked glycans are released from antibody captured glycoproteins and are directly analyzed by MALDI-TOF mass spectrometry. We hypothesize that this method can be used to identify glycan biomarkers reflective of the changes that occur during the development of hepatocellular carcinoma. In this Phase I STTR application we anticipate developing a reproducible and translatable workflow using MALDI-MS of captured proteins that can accurately detect the presence of hepatocellular carcinoma.

长期以来，糖基化的改变与糖尿病的发生和进展有关