Aberrant changes
in site-specific core fucosylation
(CF) of serum proteins contribute to cancer development and progression,
which enables them as potential diagnostic markers of tumors. An optimized
data-dependent acquisition (DDA) workflow involving isobaric tags
for relative and absolute quantitation-labeling and enrichment of
CF peptides by lens culinaris lectin was applied to identify CF of
serum proteins in a test set of patients with nonalcoholic steatohepatitis
(NASH)-related cirrhosis (N = 16) and hepatocellular
carcinoma (HCC, N = 17), respectively. A total of
624 CF peptides from 343 proteins, with 683 CF sites, were identified
in our DDA–mass spectrometry (MS) analysis. Subsequently, 19
candidate CF peptide markers were evaluated by a target parallel reaction-monitoring–MS
workflow in a validation set of 58 patients, including NASH-related
cirrhosis (N = 29), early-stage HCC (N = 21), and late-stage HCC (N = 8). Significant
changes (p < 0.01) were observed in four CF peptides
between cirrhosis and HCC, where peptide LGSFEGLVn160LTFIHLQHNR
from LUM in combination with AFP showed the best diagnostic performance
in discriminating HCC from cirrhosis, with an area under curve (AUC)
of 0.855 compared to AFP only (AUC = 0.717). This peptide in combination
with AFP also significantly improved diagnostic performance in distinguishing
early HCC from cirrhosis, with an AUC of 0.839 compared to AFP only
(AUC = 0.689). Validation of this novel promising biomarker panel
in larger cohorts should be performed