title: Elevated core-fucosylated IgG is a new marker for hepatitis B virus-related hepatocellular carcinoma.
abstract: Immunoglubulin G (IgG) and its abnormal glycosylations are associated with carcinogenesis. The present study investigates the relationship between cancer-derived IgG and clinicopathological characteristics in hepatocellular carcinoma (HCC) and assesses the value of serum N-glycosylated IgG in diagnosing and monitoring hepatitis B virus (HBV)-related HCC. Tissue microarray analysis of 90 HCC tissues showed that HCC patients with IgG immunopositivity had higher levels of core-fucosylated α fetoprotein (AFP-L3), larger tumors, and a higher incidence of portal vein tumor thrombus. HCC-derived IgG stimulated the growth of liver cancer cellsin vitro. HCC patients presented a significantly increased fraction ofLens culinarisagglutinin binding IgG (core-fucosylated IgG, IgG-L3) among total serum IgG. The clinical diagnostic performance of serum IgG-L3% was evaluated in 3 case-control studies (1 training set and 2 validation cohorts), including 293 patients with HCC, 131 with liver cirrhosis, 132 HBV carriers, and 151 healthy controls. IgG-L3% had better general diagnostic performance than AFP in the training set and validation cohort 1 (accuracy: 81.33-85.11%versus63.33-78.61%). In validation cohort 2, where we aimed to assess the efficiency of IgG-L3% in patients with AFP-negative HCC, the diagnostic accuracy of IgG-L3% was 72.54-73.60%. Finally, a longitudinal evaluation based on 31 HCC patients demonstrated that IgG-L3% decreased in 24 patients after curative surgery. The remaining 7 patients showed elevated IgG-L3% and post-operative recurrence. HCC patients with higher IgG-L3% had poor survival during a 3-year follow up. We conclude that HCC-derived IgG is correlated with progressive behavior of HCC. Therefore, elevated core-fucosylated IgG is a new diagnostic and prognostic marker in HBV-related HCC.
authors.affiliation: Department of Laboratory Medicine; Eastern Hepatobiliary Surgery Hospital; Second Military Medical University ; Shanghai, China.
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Yi
authors.affiliation: Molecular Alcohol Research in Gastroenterology, Department of Medicine II; Germany Faculty of Medicine at Mannheim; University of Heidelberg , Heidelberg, Germany.
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Weng
authors.affiliation: Department of Hepatic Surgery VI; Eastern Hepatobiliary Surgery Hospital; Second Military Medical University ; Shanghai, China.
authors.forename: Fei-Guo
authors.initials: FG
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine; Eastern Hepatobiliary Surgery Hospital; Second Military Medical University ; Shanghai, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Laboratory Medicine; Eastern Hepatobiliary Surgery Hospital; Second Military Medical University ; Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Laboratory Medicine; Eastern Hepatobiliary Surgery Hospital; Second Military Medical University ; Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Laboratory Medicine; Changzheng Hospital; Second Military Medical University ; Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Molecular Alcohol Research in Gastroenterology, Department of Medicine II; Germany Faculty of Medicine at Mannheim; University of Heidelberg , Heidelberg, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Liebe
authors.affiliation: Molecular Alcohol Research in Gastroenterology, Department of Medicine II; Germany Faculty of Medicine at Mannheim; University of Heidelberg , Heidelberg, Germany.
authors.forename: Steven
authors.initials: S
authors.lastname: Dooley
authors.affiliation: Department of Laboratory Medicine; Eastern Hepatobiliary Surgery Hospital; Second Military Medical University ; Shanghai, China.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Gao
keywords: IgG; Lens culinaris agglutinin (LCA); diagnosis; hepatocellular carcinoma (HCC); non-invasive biomarker; tissue array