Circulating biomarkers in hepatocellular carcinoma

Area of Science:

• Oncology
• Biomarker Discovery
• Hepatocellular Carcinoma Research

Background:

• Hepatocellular carcinoma (HCC) remains a significant global health challenge.
• Accurate biomarkers for diagnosis, prognosis, and therapeutic targeting are crucial for improving patient outcomes.
• Circulating tumor cells (CTCs) and protein biomarkers offer minimally invasive insights into tumor biology and burden.

Purpose of the Study:

• To determine levels of circulating cellular and protein biomarkers in HCC patients.
• To analyze the relationships between these biomarkers and clinical parameters.
• To evaluate the prognostic significance of circulating biomarkers in HCC.

Main Methods:

• Enumeration and characterization of circulating tumor cells (CTCs) using CellSearch and Isolation by Size of Epithelial Tumor Cells (ISET) techniques.
• Immunohistochemistry (IHC) for Glypican-3 (GPC3) expression in tumor biopsies and CTCs.
• Measurement of circulating caspase-cleaved and full-length cytokeratin 18 (CK18) using M30 and M65 ELISAs.

Main Results:

• CTCs were detected in 100% of patients by ISET, with GPC3-positive CTCs showing 100% concordance with tumor GPC3 expression.
• No significant correlations were found between CTC number and clinical characteristics, though trends were observed.
• Serum M30 and M65 levels significantly correlated with overall survival (OS), with M65 remaining significant in multivariate analysis.

Conclusions:

• This study is the first to detect GPC3-positive CTCs in HCC, indicating potential for targeted drug development.
• Circulating CK18 levels demonstrate significant prognostic utility for overall survival in HCC patients.
• Circulating biomarkers represent valuable tools for cancer management and therapeutic strategies in HCC.