Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA.
School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou, Jiangsu, 221116, China.
Sci Rep. 2019 Aug 9;9(1):11580. doi: 10.1038/s41598-019-48043-1.
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.
建立了一种质谱分析平台，以确定α-1酸性糖蛋白（AGP）的糖基化模式是否可用于检测不同病因（即非酒精性脂肪性肝炎[NASH]、酒精性肝病[ALC]和丙型肝炎病毒[HCV]）的肝细胞癌（HCC）的早期标志物。从 72 例 HCC 患者和 58 例肝硬化患者的 20 μL 血清中纯化的 AGP 的 MALDI-MS 分析显示，一种独特的三岩藻糖基四天线聚糖（m/z 3490.76）主要存在于 HCC 中，但在健康受试者和大多数肝硬化患者中不存在。受试者工作特征（ROC）曲线分析表明，AGP 的三岩藻糖基 N-聚糖（triFc_AGP）可区分 HCC 与肝硬化，曲线下面积（AUC）分别为 0.707、0.726 和 0.751 用于 NASH、ALC 和 HCV。当将 triFc_AGP 与 INR 和 AFP 联合使用时，该组合在检测 NASH 相关 HCC 方面具有最大的益处，与 AFP 单独检测相比，所有 NASH HCC 的 AUC 显著提高至 0.882，早期 NASH HCC 的 AUC 提高至 0.818（分别为 0.761 和 0.641）。此外，triFc_AGP 可作为监测 AFP 阴性 HCC 患者的潜在标志物。
