18 O/ 16 O labeling N-glycopeptide quantification and MRM have been performed to investigate aberrant N-glycopeptides in HBV-related liver diseases. TPLTA N 205 ITK (H5N5S1F1) and (H5N4S2F1) of IgA 2 were significantly elevated in serum from patients with HBV infection and even higher in LC, as compared with healthy donor. In contrast, the two glycopeptides of IgA 2 fell back down in HBV-related HCC. The altered N-glycopeptides might be part of a unique glycan signature indicating IgA-mediated mechanism. Graphical Abstract Highlights 18 O/ 16 O labeling N-glycopeptide quantification for 40-kDa band in HCC and LC. MRM verification of aberrant N-glycopeptides in healthy-HBV-LC-HCC cascade. TPLTA N 205 ITK (H5N5S1F1) and (H5N4S2F1) of IgA 2 change in liver diseases. Variation in two N-glycopeptides abundance not caused by protein concentration. N-glycosylation alteration has been reported in liver diseases. Characterizing N-glycopeptides that correspond to N-glycan structure with specific site information enables better understanding of the molecular pathogenesis of liver damage and cancer. Here, unbiased quantification of N-glycopeptides of a cluster of serum glycoproteins with 40–55 kDa molecular weight (40-kDa band) was investigated in hepatitis B virus (HBV)-related liver diseases. We used an N-glycopeptide method based on 18 O/ 16 O C-terminal labeling to obtain 82 comparisons of serum from patients with HBV-related hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Then, multiple reaction monitoring (MRM) was performed to quantify N-glycopeptide relative to the protein content, especially in the healthy donor-HBV-LC-HCC cascade. TPLTA N 205 ITK (H5N5S1F1) and (H5N4S2F1) corresponding to the glycopeptides of IgA 2 were significantly elevated in serum from patients with HBV infection and even higher in HBV-related LC patients, as compared with healthy donor. In contrast, the two glycopeptides of IgA 2 fell back down in HBV-related HCC patients. In addition, the variation in the abundance of two glycopeptides was not caused by its protein concentration. The altered N-glycopeptides might be part of a unique glycan signature indicating an IgA-mediated mechanism and providing potential diagnostic clues in HBV-related liver diseases.
【저자키워드】 mass spectrometry, glycomics, glycoproteomics, Liver disease, glycopeptide, IgA2, Biomarker: Diagnostic, 40-kDa Band, HBV-Related Liver Diseases,