Serum angiopoietin-2 level as a predictor of tumor invasiveness in patients with hepatocellular carcinoma

Scand J Gastroenterol. 2013 Mar;48(3):334-43. doi: 10.3109/00365521.2012.746391. Epub 2012 Dec 19.

Abstract

Background: Because hepatocellular carcinoma (HCC) has important angiogenic activity, the expression of angiopoietin-2 (Ang-2) may have a pathogenic role. The information about the influence of serum Ang-2 (sAng-2) in patients with HCC is scarce.

Aims: The aim was to assess the association between sAng-2 levels and characteristics of tumor and liver disease in patients with HCC.

Methods: sAng-2 concentrations in peripheral (sAng-2-P) and hepatic (sAng-2-H) veins were analyzed by ELISA in 33 patients with chronic liver disease who underwent a splanchnic hemodynamic study. Thirty-two patients received treatment for HCC.

Results: The median age was 61 years and 79% were male. Hepatitis C infection (70%) was the main etiology. Most patients were Child-Pugh grade A (72.7%). sAng-2-P and sAng-2-H were well correlated (r = 0.95; p < 0.0001). A significant association was found between sAng-2-H and lobar tumor extension, vascular thrombosis, BCLC staging, infiltrating pattern, abnormal alpha-fetoprotein level, fulfillment of the Milan criteria, and performance of nonsystemic treatment. sAng-2-H also showed a significant correlation with the MELD score (r = 0.49; p = 0.007), albumin (r = -0.63; p < 0.001), and HVPG (r = 0.44; p = 0.02). Eleven patients received treatment with radiofrequency ablation and eight with transarterial chemoembolization. HCC treatment did not influence the sAng-2 concentration while the necrosis response to treatment was not influenced by previous sAng-2 levels.

Conclusions: Ang-2 seems to play an important role in the angiogenic processes of HCC and its serum levels are associated with tumor characteristics and invasive behavior. Our results suggest that Ang-2 is not related with treatment response and its level is not modified by treatment.

MeSH terms

  • Aged
  • Angiopoietin-2 / blood*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • End Stage Liver Disease / blood
  • Female
  • Humans
  • Liver Cirrhosis / blood
  • Liver Neoplasms / blood*
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prospective Studies
  • Severity of Illness Index
  • Statistics, Nonparametric
  • alpha-Fetoproteins / metabolism

Substances

  • Angiopoietin-2
  • Biomarkers, Tumor
  • alpha-Fetoproteins