Program Official
Principal Investigator
Anand S
Mehta
Awardee Organization
Medical University Of South Carolina
United States
Fiscal Year
2023
Activity Code
R01
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date
NIH RePORTER
For more information, see NIH RePORTER Project 5R01CA237659-05
Translation of a biomarker panel for the early detection of hepatocellular carcinoma
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, alphafetoprotein (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.
- Singal AG, Tayob N, Mehta A, Marrero JA, Jin Q, Lau J, Parikh ND. Doylestown Plus and GALAD Demonstrate High Sensitivity for HCC Detection in Patients With Cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Apr;20(4):953-955.e2. Epub 2021 Apr 20. PMID: 33864933
- DelaCourt A, Black A, Angel P, Drake R, Hoshida Y, Singal A, Lewin D, Taouli B, Lewis S, Schwarz M, Fiel MI, Mehta AS. N-Glycosylation Patterns Correlate with Hepatocellular Carcinoma Genetic Subtypes. Molecular cancer research : MCR. 2021 Nov;19(11):1868-1877. Epub 2021 Aug 11. PMID: 34380744
- Ochoa-Rios S, Blaschke CRK, Wang M, Peterson KD, DelaCourt A, Grauzam SE, Lewin D, Angel P, Roberts LR, Drake R, Mehta AS. Analysis of N-linked Glycan Alterations in Tissue and Serum Reveals Promising Biomarkers for Intrahepatic Cholangiocarcinoma. Cancer research communications. 2023 Mar 6;3(3):383-394. doi: 10.1158/2767-9764.CRC-22-0422. eCollection 2023 Mar. PMID: 36890858
- Wang M, Singal AG, Parikh N, Kono Y, Marrero J, Mehta A. A Biomarker Panel Based upon AFP, Fucosylated Kininogen and PEG-Precipitated IgG Is Highly Accurate for the Early Detection Hepatocellular Carcinoma in Patients with Cirrhosis in Phase II and Phase III Biomarker Evaluation. Cancers. 2022 Dec 2;14. (23). PMID: 36497452
- Fujiwara N, Kobayashi M, Fobar AJ, Hoshida A, Marquez CA, Koneru B, Panda G, Taguri M, Qian T, Raman I, Li QZ, Hoshida H, Sezaki H, Kumada H, Tateishi R, Yokoo T, Yopp AC, Chung RT, Fuchs BC, Baumert TF, Marrero JA, Parikh ND, Zhu S, Singal AG, Hoshida Y. A blood-based prognostic liver secretome signature and long-term hepatocellular carcinoma risk in advanced liver fibrosis. Med (New York, N.Y.). 2021 Jul 9;2(7):836-850.e10. Epub 2021 Apr 21. PMID: 34318286
- Singal AG, Tayob N, Mehta A, Marrero JA, El-Serag H, Jin Q, Saenz de Viteri C, Fobar A, Parikh ND. GALAD demonstrates high sensitivity for HCC surveillance in a cohort of patients with cirrhosis. Hepatology (Baltimore, Md.). 2022 Mar;75(3):541-549. Epub 2021 Dec 17. PMID: 34618932
- Fujiwara N, Fobar AJ, Raman I, Li QZ, Marrero JA, Parikh ND, Singal AG, Hoshida Y. A Blood-Based Prognostic Liver Secretome Signature Predicts Long-term Risk of Hepatic Decompensation in Cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 May;20(5):e1188-e1191. Epub 2021 Mar 13. PMID: 33727162
- Wang M, Grauzam S, Bayram MF, Dressman J, DelaCourt A, Blaschke C, Liang H, Scott D, Huffman G, Black A, Ochoa-Rios S, Lewin D, Angel PM, Drake RR, Ball L, Bethard J, Castellino S, Kono Y, Kubota N, Hoshida Y, Quirk L, Yopp A, Gopal P, Singal A, Mehta AS. Spatial omics-based machine learning algorithms for the early detection of hepatocellular carcinoma. Communications medicine. 2024 Dec 3;4(1):258. PMID: 39627514
- El-Serag HB, Jin Q, Tayob N, Salem E, Luster M, Alsarraj A, Khaderi S, Singal AG, Marrero JA, Asrani SK, Kanwal F. HES V2.0 outperforms GALAD for detection of HCC: A phase 3 biomarker study in the United States. Hepatology (Baltimore, Md.). 2025 Feb 1;81(2):465-475. Epub 2024 Jun 19. PMID: 38899967
- Fujiwara N, Lopez C, Marsh TL, Raman I, Marquez CA, Paul S, Mishra SK, Kubota N, Katz C, Kanzaki H, Gonzalez M, Quirk L, Deodhar S, Selvakumar P, Raj P, Parikh ND, Roberts LR, Schwartz ME, Nguyen MH, Befeler AS, Page-Lester S, Srivastava S, Feng Z, Reddy KR, Khaderi S, Asrani SK, Kanwal F, El-Serag HB, Marrero JA, Singal AG, Hoshida Y. Phase 3 Validation of PAaM for Hepatocellular Carcinoma Risk Stratification in Cirrhosis. Gastroenterology. 2025 Mar;168(3):556-567.e7. Epub 2024 Nov 8. PMID: 39521255
- Marsh TL, Parikh ND, Roberts LR, Schwartz ME, Nguyen MH, Befeler A, Page-Lester S, Tayob N, Srivastava S, Rinaudo JA, Singal AG, Reddy KR, Marrero JA. A Phase 3 Biomarker Validation of GALAD for the Detection of Hepatocellular Carcinoma in Cirrhosis. Gastroenterology. 2025 Feb;168(2):316-326.e6. Epub 2024 Sep 16. PMID: 39293548