Translation of a biomarker panel for the early detection of hepatocellular carcinoma

用于早期检测肝细胞癌的生物标志物组的翻译

• 批准号: 10686284
• 负责人: JORGE A MARRERO
• 金额: $ 40.6万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-18 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10686284
• 关键词: Acceleration; Age; Algorithms; Alkaline Phosphatase; Area; Aspartate Transaminase; Biological Assay; Biological Markers; Blinded; Blood; Businesses; Case/Control Studies; Cirrhosis; Clinical; Clinical Laboratory Improvement Amendments; Clinical Management; Collaborations; Collection; Data; Detection; Diagnosis; Diagnostic; Discrimination; Disease; Early Diagnosis; Evaluation; Gender; Geographic Locations; Glycoproteins; Goals; Histology; Image; Individual; Industrialization; Industry; Influentials; Institution; Kininogens; Laboratories; Legal patent; Lesion by Stage; Licensing; Link; Liver Fibrosis; Logistic Regressions; Low-Molecular-Weight Kininogen; Malignant Epithelial Cell; Malignant Neoplasms; Malignant neoplasm of liver; Marketing; Measurement; Medical; Medical center; Medicare; Methods; Modeling; Patient Care; Patients; Performance; Phase; Polysaccharides; Populations at Risk; Post-Translational Protein Processing; Primary carcinoma of the liver cells; Proteins; Reagent; Receiver Operating Characteristics; Reproducibility; Research; Risk; Running; Sampling; Sensitivity and Specificity; Serum; Serum Proteins; Services; Site; South Carolina; Specialist; Support System; Technology; Testing; Texas; Time; Translating; Translations; United States Centers for Medicare and Medicaid Services; Universities; Validation; Work; alpha-Fetoproteins; biomarker identification; biomarker panel; biomarker validation; cancer diagnosis; case control; clinical diagnosis; clinical practice; clinically relevant; cohort; commercialization; design; early detection biomarkers; glycosylation; improved; liver function; multidisciplinary; novel; novel marker; prospective; regression algorithm; sample collection; testing services; tumor; ultrasound; validation studies

This application proposes to translate our identification of a biomarker panel for hepatocellular carcinoma to commercial and clinical use. We have identified a specific post-translation modification that is altered in HCC. This alteration is a shift in the composition of N-linked glycans found on proteins made in and secreted by HCC cells. Many of the proteins containing this glycan alteration have been identified and patented. Our strong preliminary evidence has shown that some of these proteins, when combined with existing biomarkers and clinical factors, have excellent discriminatory ability between those with HCC and those with cirrhosis. Importantly, our biomarker efforts have focused on the detection of early stage lesions using our current biomarker panel, which is a simple logistic regression algorithm composed of fucosylated kininogen, alpha- fetoprotein (AFP), alkaline phosphatase (ALK), aspartate aminotransferase (AST), age and gender. Called the kininogen panel, it had an area under the receiver operator curve (AUROC) of 0.97 for the differentiation of early stage HCC from cirrhosis. In an independent external validation of this panel, in three independent cohorts this panel had an AUROC of 0.92 to 0.97 in the detection of early stage HCC. Thus our enthusiasm for this biomarker panel is high. To fully understand the clinical and commercial benefits of any biomarker, a large scale clinical validation study that is appropriate powered is essential. Hence, the two goals of this application are to validate the kininogen panel for the detection of early stage HCC at the time of HCC diagnosis (Aim 1) and determine when in time an individual becomes biomarker positive prior to developing HCC (Aim 2). At the completion of these two aims, Glycotest will have validated this biomarker panel and have confidence in its performance. Glycotest's strategy is focused on commercialization of its tests as Laboratory Developed Test (LDT) service products. These tests will be marketed to and ordered by specialists who care for the patient populations at risk for liver cancers and fibrosis-cirrhosis. LDTs are tests developed and run in a single "CLIA lab" regulated by the Center for Medicare & Medicaid Services (CMS) through the Clinical Laboratory Improvement Amendments (CLIA). The LDT business model has been used successfully by many other US companies that have commercialized tests as service products in multiple disease areas. The Company will establish an internal selling and marketing capability focused initially on major influential medical centers and key opinion leader sites as well as the west coast and east coast geographical areas, and will pursue a strategy for establishing Medicare reimbursement that it has developed in collaboration with external experts.

本应用程序建议将我们对肝细胞癌生物标志物面板的鉴定转化为

项目成果

N-Glycosylation Patterns Correlate with Hepatocellular Carcinoma Genetic Subtypes.

• DOI: 10.1158/1541-7786.mcr-21-0348
• 发表时间: 2021-11
• 期刊: Molecular cancer research : MCR
• 作者: DelaCourt A;Black A;Angel P;Drake R;Hoshida Y;Singal A;Lewin D;Taouli B;Lewis S;Schwarz M;Fiel MI;Mehta AS
• 通讯作者: Mehta AS