Evaluation of AGP Fucosylation as a Marker for Hepatocellular Carcinoma of Three Different Etiologies.

Author(s): Liang J,  Zhu J,  Wang M,  Singal AG,  Odewole M,  Kagan S,  Renteria V,  Liu S,  Parikh ND,  Lubman DM

Journal: Sci Rep

Date: 2019 Aug 9

Major Program(s) or Research Group(s): GLYCO

PubMed ID: 31399619

PMC ID: PMC6689003

Abstract: A mass spectrometric analysis platform has been developed to determine whether glycosylation patterns of alpha-1 acid glycoprotein (AGP) could be used as a marker for early detection of hepatocellular carcinoma (HCC) in different etiologies, i.e. non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALC), and hepatitis C virus (HCV). MALDI-MS profiling of N-glycans of AGP purified from 20 μL of patient serum in HCC (n = 72) and liver cirrhosis (n = 58) showed that a unique trifucosylated tetra-antennary glycan (m/z 3490.76) was predominantly identified in HCCs but was absent in healthy subjects and the majority of cirrhosis patients. Receiver operation characteristic (ROC) curve analysis showed that the trifucosylated N-glycan of AGP (triFc_AGP) could differentiate HCC from cirrhosis with an area under the curve (AUC) of 0.707, 0.726 and 0.751 for NASH, ALC and HCV, respectively. When combining triFc_AGP with INR and AFP, the panel had the greatest benefit in detection of NASH-related HCCs, with a significantly improved AUC of 0.882 for all NASH HCCs and 0.818 for early NASH HCCs compared to AFP alone (0.761 and 0.641, respectively). Moreover, triFc_AGP could serve as a potential marker for monitoring AFP-negative HCC patients.