Phosphopeptidome Profiling of Human Plasma for Hepatocellular Carcinoma Biomarker Discovery.

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 reveale

SUBMITTER: Saleem S 

PROVIDER: S-EPMC12831616 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature