Article Abstract

HIF-1α and VEGF levels for monitoring hepatocellular carcinoma treatment response to transcatheter arterial chemoembolization

Authors: Kang Liu, Lin Yang, Xiao-Ming Zhang, Yi Zhou, Tao Zhu, Nan-Dong Miao, Yong-Jun Ren, Hao Xu, Xu-Li Min, Juan Peng, Ke Yang, Shi Yang


Background: The purpose of the present study was to investigate the use of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels to monitor the treatment response to transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC).
Methods: A total of 41 consecutive HCC patients underwent TACE were enrolled into this study. The serum levels of HIF-1α and VEGF were measured using enzyme-linked immunosorbent assays (ELISAs) 1 day before, and 1, 7 and 28 days after TACE therapy. The overall tumor response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors criteria. Patients with a complete response or partial response comprised the responding group, whereas those with stable disease or progressive disease comprised the non-responding group. The differences in serum HIF-1α and VEGF levels before and after TACE therapy were subjected to analysis of nonparametric test, while correlations between serum HIF-1α and VEGF levels were examined using Pearson’s correlation analysis. Receiver-operating characteristic (ROC) curve was applied to analyze the evaluation value of factors for the response of TACE on the treatment of HCC. P<0.05 was considered statistically significant.
Results: In the present study, the serum levels of HIF-1α correlated positively with the serum levels of VEGF 1 day before TACE (r=0.546, P=0.000). The levels of HIF-1α and VEGF 1 day before, and 1, 7 and 28 days after TACE were significantly different, respectively (χ2=90.688, P=0.000 and χ2=45.585, P=0.000). The levels of the HIF-1α and VEGF increased markedly on day 1 and 7 after TACE and recovered to the pre-TACE level on day 28 after TACE. The levels of serum VEGF in responder group 28 days after TACE were significantly lower than those in non-responder group (Z=2.774, P=0.006), but the difference of HIF-1α levels between the two groups was not significant (Z=1.905, P=0.057). ROC curve analysis indicated that the sensitivity and specificity were 76.9% and 78.6%, when the threshold value was set at VEGF =254.5 pg/mL for predicting the response of TACE in patients with HCC; the corresponding area under the curve (AUC) was 0.772, respectively.
Conclusions: The levels of both HIF-1α and VEGF in patients with HCC after TACE exhibit dynamic changes. However, HIF-1α and VEGF may be insufficient for predicting tumor response to TACE treatment.