缺氧诱导因子 1α 和血管内皮生长因子作为经动脉化疗栓塞治疗的肝细胞癌患者的预后生物标志物。

HIF-1α and VEGF as prognostic biomarkers in hepatocellular carcinoma patients treated with transarterial chemoembolization.

机构信息

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, Padova, Italy.

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.

出版信息

Dig Liver Dis. 2024 May;56(5):872-879. doi: 10.1016/j.dld.2023.09.019. Epub 2023 Sep 30.

DOI:10.1016/j.dld.2023.09.019

PMID:37783655

Abstract

BACKGROUND

Neoangiogenesis plays a crucial role in the progression of hepatocellular carcinoma (HCC), and concerns have been raised about the role of neoangiogenesis on the effectiveness of transarterial chemoembolization (TACE).

AIM

In this study, we aimed to evaluate Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Inducible Factor-1α (HIF-1α) as circulating prognostic biomarkers in HCC patients treated with TACE.

METHODS

Blood samples were collected from 163 patients before (t) and four weeks after TACE (t).

RESULTS

Higher levels of VEGF after TACE were demonstrated (264.0 [78.7-450.8] vs. 278.6 [95.0-576.6] pg/mL; p < 0.0001). Responders to TACE had lower levels of VEGF than non-responders both at t (200.0 [58.9-415.8] vs. 406.6 [181.4-558.6] pg/mL; p = 0.006) and at t (257.3 [68.5-528.6] vs. 425.9 [245.2-808.3] pg/mL; p = 0.003), and in both groups there was an increase in VEGF compared to measurements before treatment (p = 0.001 and p = 0.005, respectively). VEGF was not associated with overall survival (OS), while patients with HIF-1α ≤ 0.49 ng/mL showed better prognosis (median OS 28.0 months [95% CI 19.7-36.3] vs. 17.0 months [95% CI 11.1-22.9]; p = 0.01). Moreover, HIF-1α was identified as an independent prognostic parameter.

CONCLUSIONS

VEGF and HIF-1α can be considered useful prognostic biomarkers in HCC patients treated with TACE.

摘要

背景

新生血管形成在肝细胞癌（HCC）的进展中起着至关重要的作用，人们对新生血管形成对经动脉化疗栓塞（TACE）疗效的影响表示关注。

目的

本研究旨在评估血管内皮生长因子（VEGF）和缺氧诱导因子-1α（HIF-1α）作为接受 TACE 治疗的 HCC 患者的循环预后生物标志物。

方法

从 163 例患者中采集治疗前（t）和 TACE 后 4 周（t）的血样。

结果

TACE 后 VEGF 水平升高（264.0 [78.7-450.8] 与 278.6 [95.0-576.6] pg/mL；p < 0.0001）。TACE 反应者的 VEGF 水平低于无反应者，无论是在 t 时（200.0 [58.9-415.8] 与 406.6 [181.4-558.6] pg/mL；p = 0.006）还是在 t 时（257.3 [68.5-528.6] 与 425.9 [245.2-808.3] pg/mL；p = 0.003），并且与治疗前的测量值相比，两组 VEGF 均有所增加（p = 0.001 和 p = 0.005）。VEGF 与总生存期（OS）无关，而 HIF-1α ≤ 0.49 ng/mL 的患者预后更好（中位 OS 28.0 个月[95%CI 19.7-36.3] 与 17.0 个月[95%CI 11.1-22.9]；p = 0.01）。此外，HIF-1α 被确定为独立的预后参数。