Clinical and prognostic significance of circulating levels of angiopoietin-1 and angiopoietin-2 in hepatocellular carcinoma

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) play critical roles in angiogenesis in hepatocellular carcinoma (HCC). In addition, recent data suggest that Ang-1/Ang-2 are involved in regulating the immune response. The aim of our study was to explore the clinical prognostic significance of plasma Ang-1 and Ang-2 in HCC. We prospectively enrolled and collected data and blood samples from 767 HCC patients treated at MD Anderson Cancer Center between 2001 and 2014. Controls consisted of cirrhotic patients (n = 75) and healthy volunteers (n = 200). The cutoff value was the median level of each angiogenic factor. Overall survival (OS) was estimated by Kaplan-Meier curves and compared by the log-rank test. Higher plasma Ang-2 was significantly associated with advanced clinicopathologic features of advanced HCC and lower OS. Median OS was 61.8 months (95% confidence interval [CI], 45.1-78.5 months) for low Ang-2 compared with 28.5 months (95% CI, 24.8-32.1 months) for high Ang-2 (p < 0.001). In contrast, higher Ang-1 was associated with longer OS. Median OS was 37.2 months (95% CI, 31.0-43.4 months) for high Ang-1 compared with 26.2 months (95% CI, 22.2-30.3 months) for those with low Ang-1 (p = 0.043). In conclusion, our findings indicate that plasma Ang-1 and Ang-2 levels are potential diagnostic and prognostic biomarkers in HCC.