Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) frequently invades the portal vein, leading to early recurrence and a poor prognosis. However, the mechanisms underlying this invasion remain unclear. In this study, we aimed to detect portal vein circulating tumor cells (CTCs) using a Glypican-3-positive detection method and evaluate their prognostic significance. METHODS: This prospective study included 146 patients with HCC who underwent open anatomical hepatectomy. Blood samples from the peripheral, portal, and hepatic veins were collected intraoperatively, and CTCs were detected using magnetic enrichment and flow cytometry. Programmed cell death ligand 1 (PD-L1) expression in portal CTCs was evaluated in 40 patients. RESULTS: Portal vein CTCs were detected in 45.8% of cases, more frequently than hepatic vein CTCs (p = 0.031). Portal vein CTC positivity correlated with microscopic portal vein invasion (p < 0.001), poorer disease-free survival (p = 0.014), and overall survival (p = 0.001). PD-L1-positive portal vein CTCs were observed in 13 of 40 cases (32.5%) and were significantly associated with poorer prognosis (p = 0.001). CONCLUSIONS: Portal vein CTCs are significant predictors of portal vein invasion, recurrence, and survival in HCC. PD-L1-positive portal vein CTCs may contribute to immune evasion and tumor progression. These findings suggest that portal vein CTCs are valuable prognostic biomarkers and potential therapeutic targets.