Unveiling Endogenous Serum Peptides as Potential Biomarkers for Hepatocellular Carcinoma in Patients with Liver Cirrhosis

Hepatocellular carcinoma (HCC) is a leading cause of
cancer-related
deaths worldwide, mainly associated with liver cirrhosis. Current
diagnostic methods for HCC have limited sensitivity and specificity,
highlighting the need for improved early detection and intervention.
In this study, we used a comprehensive approach involving endogenous
peptidome along with bioinformatics analysis to identify and evaluate
potential biomarkers for HCC. Serum samples from 40 subjects, comprising
20 HCC cases and 20 patients with liver cirrhosis (CIRR), were analyzed.
Among 2568 endogenous peptides, 67 showed significant differential
expression between the HCC vs CIRR. Further analysis revealed three
endogenous peptides (VMHE­ALHNH­YTQK­SLSL­SPG,
NRFTQ­KSLSL­SPG, and SARQ­STLD­KEL) that showed
far better performance compared to AFP in terms of area under the
receiver operating characteristic curve (AUC), showcasing their potential
as biomarkers for HCC. Additionally, endogenous peptide IAVEW­ESNGQ­PENNY­KT
that belongs to the precursor protein Immunoglobulin heavy constant
gamma 4 was detected in 100% of the HCC group and completely absent
in the CIRR group, suggesting a promising diagnostic biomarker. Gene
ontology and pathway analysis revealed the potential involvement of
these dysregulated peptides in HCC. These findings provide valuable
insights into the molecular basis of HCC and may contribute to the
development of improved diagnostic methods and therapeutic targets
for HCC.