Association between Vessels Encapsulating Tumor Clusters and Circulating Tumor Cells in Hepatocellular Carcinoma: Clinical Evidence and Risk Model Development

Background: Vessels encapsulating tumor clusters (VETC) and circulating tumor cells (CTCs) are recognized as emerging potential biomarkers in hepatocellular carcinoma (HCC), yet the underlying connection between them is not fully elucidated. This study aims to investigate the association between VETC and CTCs and evaluate their potential clinical utility. Methods: This retrospective cohort study (NCT05297955) included 165 HCC patients who underwent curative hepatic resection. VETC was identified via CD34 immunohistochemical staining, and preoperative CTC levels were measured using the CellSearch platform. Propensity score matching (PSM) adjusted for confounders, and LASSO-Cox regression was used to develop a prognostic model. Results: VETC-positive tumors were significantly associated with increased disease progression and shorter overall survival (OS) and disease-free survival (DFS). Elevated preoperative CTC counts showed a robust correlation with the VETC phenotype. The co-occurrence of VETC and CTCs emerged as a powerful prognostic indicator for both OS and DFS. A novel DFS prediction model, Vrisk, incorporating VETC, CTC, and four additional factors, demonstrated superior predictive performance compared to conventional staging systems. Conclusions: The study establishes a strong association between VETC, elevated CTC levels, and poorer prognosis in HCC, providing critical insights into their functional roles and potential as biomarkers for clinical applications.