Angiogenic inflammation and formation of necrosis in the tumor microenvironment influence patient survival after radical surgery for de novo hepatocellular carcinoma in non-cirrhosis

World J Surg Oncol. 2019 Dec 12;17(1):217. doi: 10.1186/s12957-019-1756-8.

Abstract

Background: Tumor escape mechanisms mediated in the tumor microenvironment can significantly reduce the capacity of the anti-tumor function of the immune system. TIE2-expressing monocytes (TEMs), related angiopoietins, and tumor necrosis are considered to have a key role in this process. We aimed to investigate the abundance and clinical significance of these biomarkers in hepatocellular carcinoma (HCC).

Methods: In this retrospective study, 58 HCC patients received surgery with a curative intent. The abundance of TEMs, angiopoietin-1 and -2 were detected in tumor specimens of the HCC patients (n = 58), and together with the occurrence of histologic tumor necrosis, were associated with established clinicopathological characteristics and survival.

Results: Patients with HCC characterized by necrosis and TEMs revealed reduced both overall survival and recurrence-free survival (all p < 0.05). Angiopoietins and TEMs were associated with metastatic and recurrent HCC. Furthermore, the formation of histologic tumor necrosis was associated with advanced tumor stage and density of TEMs (all p < 0.05).

Conclusions: Histologic tumor necrosis, TEMs, and related angiopoietins were associated with multiple HCC parameters and patient survival. The tumor necrosis-TEM-angiopoietin axis may offer a novel diagnostic modality to predict patient outcome after surgery for HCC.

Keywords: Angiogenesis; Angiopoietins; Hepatocellular carcinoma; Prognosis; TIE2-expressing monocytes; Tumor necrosis; Tumor-infiltrating macrophages.

MeSH terms

  • Angiopoietin-1 / metabolism
  • Angiopoietin-2 / metabolism
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / immunology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Liver Neoplasms / immunology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / pathology*
  • Necrosis
  • Neoplasm Grading
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • Receptor, TIE-2 / metabolism
  • Retrospective Studies
  • Tumor Escape
  • Tumor Microenvironment

Substances

  • ANGPT1 protein, human
  • ANGPT2 protein, human
  • Angiopoietin-1
  • Angiopoietin-2
  • Biomarkers, Tumor
  • Receptor, TIE-2
  • TEK protein, human