ArticleJournal of proteome research2026
Phosphopeptidome Profiling of Human Plasma for Hepatocellular Carcinoma Biomarker Discovery.
Article in Journal of proteome research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality, and current biomarkers such as alpha-fetoprotein (AFP) lack diagnostic accuracy. Here, we report the first comprehensive profiling of the plasma endogenous phosphopeptidome in HCC, cirrhosis, and healthy controls using a digestion-free LC-MS/MS workflow. From 60 plasma samples, 1,365 phosphopeptides corresponding to 549 proteins were identified and quantified. Among these, the statherin-derived peptide DSSEEKFLR demonstrated outstanding discrimination between HCC and cirrhosis (AUC = 0.968), outperforming AFP (AUC = 0.648). Additional peptides, including PPGAPHTEEEGAE (NST1), YEYDELPAKDD (C4A), SLPGESEEMMEEVD (ITIH4), and VSLGSPSGEVSHPRKT (AHSG), also showed high accuracy (AUC > 0.80). Functional enrichment revealed perturbations in acute-phase response, coagulation, lipid metabolism, and LXR/RXR signaling. Collectively, this work defines a novel plasma phosphopeptide signature that reflects disease-specific proteolytic and phosphorylation dynamics, providing a foundation for developing biomarkers for early detection and clinical monitoring of HCC.
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