Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma

Background: We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort. Methods: In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS). Results: Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis. Conclusion: High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.