Serial serum VEGF-A, angiopoietin-2, and endostatin measurements in cirrhotic patients with hepatocellular carcinoma treated by transcatheter arterial chemoembolization

Abstract

Vascular endothelial growth factor (VEGF), angiopoietin-2, and endostatin have been reported to be related with angiogenesis of hepatocellular carcinoma (HCC). The potential feasibility of serial serum VEGF-A, angiopoietin-2, and endostatin measurements in cirrhotic patients with HCC treated by transcatheter arterial chemoembolization (TACE) was investigated. VEGF-A, angiopoietin-2, and endostatin serum level were determined by enzyme-linked immunosorbent assay 1 day before and 7 days after TACE in 40 patients. Then they were followed up for 3 months. The results showed that TACE could cause significant increase of VEGF-A (p < 0.01) and angiopoietin-2 (p = 0.01); whereas there was no significant change of endostatin (p > 0.1). Twenty-five patients with rapid growth of HCC within 3 months after TACE had higher proportion of American Joint Committee on Cancer HCC staging >II and higher increase of VEGF-A after TACE than 15 patients without rapid growth (all p < 0.05). Stepwise logistic regression analysis revealed that VEGF-A >16.7 pg/mL 7 days after TACE selected by receiver operating characteristic curve analysis (p < 0.05) was the only independent predictor for rapid growth of HCC (odds ratio 6.33, 95% confidence interval: upper 26, lower 1.54, p < 0.05; sensitivity 76%, specificity 66.7%, accuracy 72.5%, positive predictive level 79.2%, negative predictive level 62.5%, p < 0.01). In conclusion, significant increases of serum level VEGF-A and angiopoietin-2 after TACE have been demonstrated from this study. Therefore, serial VEGF-A level 1 day before and 7 days after TACE may be used to predict rapid HCC growth.

Figure 1

(A–C) Comparison of the differences of VEGF‐A (1A), angiopoietin‐2 (1B), and endostatin (1C) levels between patients with and without rapid growth of hepatocellular carcinoma. There was a significant difference in VEGF‐A levels (p < 0.05). Data obtained 7 days after transcatheter arterial chemoembolization minus data obtained before transcatheter arterial chemoembolization were used to calculate the differences of data in serial determinations. VEGF‐A = vascular endothelial growth factor‐A.

Figure 2

A receiver operating characteristic curve was used to establish the cutoff level of increased vascular endothelial growth factor‐A level 7 days after transcatheter arterial chemoembolization to predict rapid growth of hepatocellular carcinoma within 3 months after transcatheter arterial chemoembolization with maximal diagnostic accuracy (p < 0.05).