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Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC.
Wang, Mengjun; Sanda, Miloslav; Comunale, Mary Ann; Herrera, Harmin; Swindell, Charles; Kono, Yuko; Singal, Amit G; Marrero, Jorge; Block, Timothy; Goldman, Radoslav; Mehta, Anand.
Afiliación
  • Wang M; Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Medical University of South Carolina, Charleston, South Carolina.
  • Sanda M; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.
  • Comunale MA; Department of Microbiology and Immunology, Drexel University, Philadelphia, Pennsylvania.
  • Herrera H; Department of Microbiology and Immunology, Drexel University, Philadelphia, Pennsylvania.
  • Swindell C; Glycotest, Inc, New York, New York.
  • Kono Y; Division of Gastroenterology and Hepatology, University of California, San Diego, California.
  • Singal AG; Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas.
  • Marrero J; Division of Digestive and Liver Diseases, University of Texas Southwestern, Dallas, Texas.
  • Block T; The Baruch S. Blumberg Institute, Doylestown, Pennsylvania.
  • Goldman R; Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.
  • Mehta A; Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Medical University of South Carolina, Charleston, South Carolina. mehtaa@musc.edu.
Cancer Epidemiol Biomarkers Prev ; 26(5): 795-803, 2017 05.
Article en En | MEDLINE | ID: mdl-28223431
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. Cancer Epidemiol Biomarkers Prev; 26(5); 795-803. ©2017 AACR.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Algoritmos / Biomarcadores de Tumor / Quininógenos / Carcinoma Hepatocelular / Detección Precoz del Cáncer / Neoplasias Hepáticas Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Aged / Female / Humans / Male / Middle aged País/Región como asunto: America do norte Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Asunto de la revista: BIOQUIMICA / EPIDEMIOLOGIA / NEOPLASIAS Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Algoritmos / Biomarcadores de Tumor / Quininógenos / Carcinoma Hepatocelular / Detección Precoz del Cáncer / Neoplasias Hepáticas Tipo de estudio: Diagnostic_studies / Prognostic_studies / Screening_studies Límite: Aged / Female / Humans / Male / Middle aged País/Región como asunto: America do norte Idioma: En Revista: Cancer Epidemiol Biomarkers Prev Asunto de la revista: BIOQUIMICA / EPIDEMIOLOGIA / NEOPLASIAS Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos