Dynamics of endothelial progenitor cells in patients with advanced hepatocellular carcinoma

Abstract

Background and aims: Circulating endothelial progenitor cells (EPC) predict tumor vascularization and disease progression, but limited information is available on their dynamics in hepatocellular carcinoma (HCC) undergoing systemic treatment.

Methods: We prospectively analyzed different populations of EPC in 16 patients with advanced HCC receiving sorafenib. Patients were studied before therapy (T0, n = 16) and after two (T2, n = 12) and eight weeks (T8, n = 8), using high-performance flow-cytometry. The tumor response at T8 was categorized as progressive disease (PD) or clinical benefit (CB, all other responses).

Results: At T0, higher levels of CD34⁺CD133⁺KDR⁺ and CD34⁺KDR⁺ were observed in patients with alpha-fetoprotein ≥400 ng/ml or non-viral liver disease, whereas CD34⁺CD133⁺KDR⁺ cells were virtually absent in patients with vascular invasion. CD34⁺KDR⁺ and CD34⁺CD133⁺KDR⁺ were directly correlated with platelet count. Frequencies of all populations of EPC declined in patients receiving sorafenib. Levels of CD34⁺CD133⁺ were higher at T0 in patients with CB compared to patients with PD. In patients belonging to the CB group CD34⁺KDR⁺ cells at T0 were directly correlated to platelet count.

Conclusion: In patients with advanced HCC, EPC are directly correlated with platelet count, suggesting a common activation of selected bone marrow pathways. Levels of a CD34⁺KDR⁺ are higher at baseline in patients responding to sorafenib.

Keywords: Angiogenesis; Liver cancer; Sorafenib; Systemic therapy.