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Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC
Journal article   Open access   Peer reviewed

Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC

Mengjun Wang, Miloslav Sanda, Mary Ann Comunale, Harmin Herrera, Charles Swindell, Yuko Kono, Amit G. Singal, Jorge Marrero, Timothy Block, Radoslav Goldman, …
Cancer epidemiology, biomarkers & prevention, v 26(5), pp 795-803
01 May 2017
PMID: 28223431
url
https://doi.org/10.1158/1055-9965.epi-16-0974View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Life Sciences & Biomedicine Oncology Public, Environmental & Occupational Health Science & Technology
Background: Hepatocellular carcinoma (HCC) has the greatest increase in mortality among all solids tumors in the United States related to low rates of early tumor detection. Development of noninvasive biomarkers for the early detection of HCC may reduce HCC-related mortality. Methods: We have developed an algorithm that combines routinely observed clinical values into a single equation that in a study of >3,000 patients from 5 independent sites improved detection of HCC as compared with the currently used biomarker, alpha-fetoprotein (AFP), by 4% to 20%. However, this algorithm had limited benefit in those with AFP <20 ng/mL. To that end, we have developed a secondary algorithm that incorporates a marker, fucosylated kininogen, to improve the detection of HCC, especially in those with AFP <20 ng/mL and early-stage disease. Results: The ability to detect early-stage AFP-negative (AFP <20 ng/mL) HCC increased from 0% (AFP alone) to 89% (for the new algorithm). Glycan analysis revealed that kininogen has several glycan modifications that have been associated with HCC, but often not with specific proteins, including increased levels of core and outer-arm fucosylation and increased branching. Conclusions: An algorithm combining fucosylated kininogen, AFP, and clinical characteristics is highly accurate for early HCC detection. Impact: Our biomarker algorithm could significantly improve early HCC detection and curative treatment eligibility in patients with cirrhosis. (C) 2017 AACR.

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Collaboration types
Domestic collaboration
Web of Science research areas
Oncology
Public, Environmental & Occupational Health
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