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

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

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 (t0) and four weeks after TACE (t1).

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 t0 (200.0 [58.9-415.8] vs. 406.6 [181.4-558.6] pg/mL; p = 0.006) and at t1 (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.

Keywords: Angiogenesis; Liver cancer; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / metabolism
  • Carcinoma, Hepatocellular* / blood
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / therapy
  • Chemoembolization, Therapeutic* / methods
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit* / blood
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Liver Neoplasms* / blood
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / therapy
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Vascular Endothelial Growth Factor A* / blood

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A
  • Biomarkers, Tumor
  • HIF1A protein, human
  • VEGFA protein, human