Mary Ann Comunale1, Mengjun Wang2, Nikhil Anbarasan3, Lucy Betesh2, Aykan Karabudak3, Ethan Moritz3, Karthik Devarajan4, Jorge Marrero5, Timothy M Block2, Anand Mehta2. 1. Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA 18901, USA. 2. Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA, USA. 3. Institute for Hepatitis and Virus Research, Doylestown, PA, USA. 4. Fox Chase Cancer Center, Philadelphia, PA, USA. 5. Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
Abstract
PURPOSE: Hepatocellular carcinoma (HCC) is a primary cancer of the liver that is predominantly the result of infection with a hepatotropic virus such as hepatitis B virus or hepatitis C virus. As liver cancer is often asymptomatic, the development of sensitive noninvasive biomarkers is needed for early detection and improved survival. EXPERIMENTAL DESIGN: We have previously identified alterations in the N-linked glycosylation of serum proteins with the development of HCC and identified many of the proteins that contained the altered glycosylation. In the current study, we compared the ability of the identified proteins to diagnose HCC with the total serum glycan analysis. RESULTS: Surprisingly, glycan analysis of total serum had the greatest ability to distinguish HCC from cirrhosis with an AUROC of 0.851, a sensitivity of 73% at a specificity of 88%. When total glycan sequencing was combined with alpha-fetoprotein (AFP), the sensitivity increased to 95% at a specificity of 90%. CONCLUSION AND CLINICAL RELEVANCE: Changes in glycosylation as detected in whole serum could be used to diagnose HCC with greater sensitivity and specificity than that observed through the analysis of specific protein glycoforms or protein levels. Such an assay could have value in the management of those at risk for the development of HCC.
PURPOSE:Hepatocellular carcinoma (HCC) is a primary cancer of the liver that is predominantly the result of infection with a hepatotropic virus such as hepatitis B virus or hepatitis C virus. As liver cancer is often asymptomatic, the development of sensitive noninvasive biomarkers is needed for early detection and improved survival. EXPERIMENTAL DESIGN: We have previously identified alterations in the N-linked glycosylation of serum proteins with the development of HCC and identified many of the proteins that contained the altered glycosylation. In the current study, we compared the ability of the identified proteins to diagnose HCC with the total serum glycan analysis. RESULTS: Surprisingly, glycan analysis of total serum had the greatest ability to distinguish HCC from cirrhosis with an AUROC of 0.851, a sensitivity of 73% at a specificity of 88%. When total glycan sequencing was combined with alpha-fetoprotein (AFP), the sensitivity increased to 95% at a specificity of 90%. CONCLUSION AND CLINICAL RELEVANCE: Changes in glycosylation as detected in whole serum could be used to diagnose HCC with greater sensitivity and specificity than that observed through the analysis of specific protein glycoforms or protein levels. Such an assay could have value in the management of those at risk for the development of HCC.
Authors: Jorge A Marrero; Patrick R Romano; Olga Nikolaeva; Laura Steel; Anand Mehta; Claus J Fimmel; Mary Ann Comunale; Anthony D'Amelio; Anna S Lok; Timothy M Block Journal: J Hepatol Date: 2005-06-28 Impact factor: 25.083
Authors: Mary Ann Comunale; Melissa Lowman; Ronald E Long; Jonathan Krakover; Ramila Philip; Steven Seeholzer; Alison A Evans; Hie-Won L Hann; Timothy M Block; Anand S Mehta Journal: J Proteome Res Date: 2006-02 Impact factor: 4.466
Authors: N Yamashiki; T Seki; M Wakabayashi; T Nakagawa; M Imamura; T Tamai; A Nishimura; K Inoue; A Okamura; S Arita; K Harada Journal: Oncol Rep Date: 1999 Nov-Dec Impact factor: 3.906
Authors: Ashwin Balagopal; Frances H Philp; Jacquie Astemborski; Timothy M Block; Anand Mehta; Ronald Long; Gregory D Kirk; Shruti H Mehta; Andrea L Cox; David L Thomas; Stuart C Ray Journal: Gastroenterology Date: 2008-03-29 Impact factor: 22.682
Authors: Radka Saldova; Louise Royle; Catherine M Radcliffe; Umi M Abd Hamid; Rachel Evans; James N Arnold; Rosamonde E Banks; Richard Hutson; David J Harvey; Robin Antrobus; Stefana M Petrescu; Raymond A Dwek; Pauline M Rudd Journal: Glycobiology Date: 2007-09-20 Impact factor: 4.313
Authors: Anand S Mehta; Ronald E Long; Mary Ann Comunale; Mengjun Wang; Lucy Rodemich; Jonathan Krakover; Ramila Philip; Jorge A Marrero; Raymond A Dwek; Timothy M Block Journal: J Virol Date: 2007-11-28 Impact factor: 5.103
Authors: Connor A West; Mengjun Wang; Harmin Herrera; Hongyan Liang; Alyson Black; Peggi M Angel; Richard R Drake; Anand S Mehta Journal: J Proteome Res Date: 2018-09-05 Impact factor: 4.466