Dynamics of endothelial progenitor cells in patients with advanced hepatocellular carcinoma

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.

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).

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.

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.