Lin Zhi-Huan, Jiang Jun-Rong, Ma Xiao-Kun, Chen Jie, Li He-Ping, Li Xing, Wu Xiang-Yuan, Huang Ming-Sheng, Lin Qu
Department of Medical Oncology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China.
Department of Medical Oncology, The Eastern Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China.
Clin Exp Med. 2021 Feb;21(1):109-120. doi: 10.1007/s10238-020-00667-8. Epub 2020 Oct 9.
Transarterial chemoembolization (TACE) induces a change in serum HIF-1α level in patients with hepatocellular carcinoma (HCC). This study investigated the prognostic value of change in serum HIF-1α 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-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) by enzyme-linked immunosorbent assay (ELISA). Serum HIF-1α change was calculated as follows: ∆HIF-1α = (HIF-1α (pre-TACE) - HIF-1α (post-TACE))/HIF-1α (pre-TACE). Likewise, serum VEG-F change was calculated as follows: ∆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 ∆HIF-1α group (< 0.25) and the high ∆HIF-1α group (> 0.25). After TACE treatment, HIF-1α 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 ∆HIF-1α 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 ∆HIF-1α 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 ∆HIF-1α 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 ∆HIF-1α group. The change in serum HIF-1α level following TACE is a prognostic factor associated with the TACE treatment response, PFS, and OS in HCC patients following TACE.
经动脉化疗栓塞术（TACE）可导致肝细胞癌（HCC）患者血清缺氧诱导因子-1α（HIF-1α）水平发生变化。本研究探讨了TACE治疗后血清HIF-1α变化对HCC患者的预后价值。共纳入61例接受TACE治疗的肝细胞癌患者。在TACE治疗前1周内及治疗后采集外周血样本，采用酶联免疫吸附测定（ELISA）法测定血清缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子-A（VEGF-A）水平。血清HIF-1α变化计算如下：∆HIF-1α =（TACE治疗前HIF-1α - TACE治疗后HIF-1α）/TACE治疗前HIF-1α。同样，血清VEG-F变化计算如下：∆VEG-F =（TACE治疗前VEG-F - TACE治疗后VEG-F）/TACE治疗前VEG-F。根据受试者工作特征分析中最大约登指数确定的临界值（0.25），将患者分为低∆HIF-1α组（<0.25）和高∆HIF-1α组（>0.25）。TACE治疗后，HIF-1α显著降低（TACE治疗前1901.62 pg/ml vs. TACE治疗后621.82 pg/ml，P<0.01），但VEGF-A显著升高（TACE治疗前60.80 pg/ml vs. TACE治疗后143.81 pg/ml，P<0.01）。多因素logistic回归分析表明，∆HIF-1α是TACE治疗反应的预后因素（比值比[OR]=58.09，95%置信区间[CI]：1.59 - 2127.32，P=0.027）。此外，多因素Cox回归分析显示，∆HIF-1α是无进展生存期（PFS）的预后因素（风险比[HR]=0.30，95%CI：0.14 - 0.66，P=0.003）和总生存期（OS）的预后因素（估计HR=0.38，95%CI：0.16 - 0.93，P=0.034）。Kaplan-Meier生存分析显示，高∆HIF-1α组比低∆HIF-1α组更有可能具有更长的PFS（对数秩检验，P=0.004）和OS（对数秩检验，P=0.002）。TACE治疗后血清HIF-1α水平的变化是与TACE治疗反应、HCC患者TACE治疗后的PFS和OS相关的预后因素。
