title: Total serum glycan analysis is superior to lectin-FLISA for the early detection of hepatocellular carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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%.
  
  
  CONCLUSIONS
  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.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA 18901, USA.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Comunale
authors.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA, USA.
authors.forename: Mengjun
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute for Hepatitis and Virus Research, Doylestown, PA, USA.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Anbarasan
authors.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA, USA.
authors.forename: Lucy
authors.initials: L
authors.lastname: Betesh
authors.affiliation: Institute for Hepatitis and Virus Research, Doylestown, PA, USA.
authors.forename: Aykan
authors.initials: A
authors.lastname: Karabudak
authors.affiliation: Institute for Hepatitis and Virus Research, Doylestown, PA, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Moritz
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Karthik
authors.initials: K
authors.lastname: Devarajan
authors.affiliation: Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Marrero
authors.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Block
authors.affiliation: Department of Microbiology and Immunology, Drexel Institute for Biotechnology and Virology, Drexel University College of Medicine, Doylestown, PA, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Mehta
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis* / Q000821:virology; D055088:Early Detection of Cancer / Q000379:methods*; D016174:Hepacivirus / Q000502:physiology; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D007118:Immunoassay; D037102:Lectins / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000821:virology; D011134:Polysaccharides / Q000097:blood
chemical_list: D037102:Lectins; D011134:Polysaccharides
keywords: Cirrhosis; Glycomics; Hepatitis B virus; Hepatitis C virus; Hepatocellular carcinoma