Prognostic value of serum HIF-1α change following transarterial chemoembolization in hepatocellular carcinoma

Transarterial chemoembolization (TACE) induces a change in serum HIF-1 alpha level in patients with hepatocellular carcinoma (HCC). This study investigated the prognostic value of change in serum HIF-1 alpha following TACE treatment in HCC patients. A total of 61 hepatocellular carcinoma patients treated with TACE were included. Peripheral blood samples were collected within 1 week before and after TACE to determine the serum levels of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor-A (VEGF-A) by enzyme-linked immunosorbent assay (ELISA). Serum HIF-1 alpha change was calculated as follows: increment HIF-1 alpha = (HIF-1 alpha (pre-TACE) - HIF-1 alpha (post-TACE))/HIF-1 alpha (pre-TACE). Likewise, serum VEG-F change was calculated as follows: increment VEG-F = (VEG-F (pre-TACE) - VEG-F(post-TACE))/VEG-F (pre-TACE). Based on the cutoffs (0.25) determined by the maximum Youden's index in receiver operating characteristic analysis, the patients were grouped into the low increment HIF-1 alpha group (< 0.25) and the high increment HIF-1 alpha group (> 0.25). After TACE treatment, HIF-1 alpha was significantly decreased (pre-TACE 1901.62 vs. post-TACE 621.82 pg/ml,P < 0.01) but VEGF-A was significantly increased (pre-TACE 60.80 vs. post-TACE 143.81 pg/ml,P < 0.01). Multivariate logistic regression analysis demonstrated that increment HIF-1 alpha was a prognostic factor (OR = 58.09, 95% CI: 1.59-2127.32, P = 0.027) for the TACE treatment response. Furthermore, multivariate Cox regression analysis revealed that increment HIF-1 alpha was a prognostic factor for progression-free survival (PFS) (HR = 0.30, 95% CI: 0.14-0.66,P = 0.003) and overall survival (OS) (estimated HR = 0.38, 95% CI: 0.16-0.93,P = 0.034). Kaplan-Meier survival analysis showed that the high increment HIF-1 alpha group was more likely to have longer PFS (log-rank test,P = 0.004) and OS (log-rank test,P = 0.002) than the low increment HIF-1 alpha group. The change in serum HIF-1 alpha level following TACE is a prognostic factor associated with the TACE treatment response, PFS, and OS in HCC patients following TACE.