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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

基本信息

批准号：
10020367
负责人：
JORGE A MARRERO
金额：
$ 51.89万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
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/10020367
关键词：
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 Kininogens Laboratories Legal patent Lesion by Stage 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 Modification Patient Care Patients Performance Phase Polysaccharides Populations at Risk 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 Ultrasonography United States Centers for Medicare and Medicaid Services Universities Validation Work alpha-Fetoproteins base biomarker panel 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 validation studies

项目摘要

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