Angiopoietin-2 as a Prognostic Factor in Patients with Incurable Stage IV Colorectal Cancer

J Gastrointest Cancer. 2021 Mar;52(1):237-242. doi: 10.1007/s12029-020-00392-1.


Purpose: Angiopoietin (Ang), a ligand of the endothelium-specific receptor Tie-2 system, is associated with tumor growth and progression that depend on angiogenesis. The present study aimed to investigate the predictive potential of angiopoietin factors in incurable stage IV colorectal cancer (CRC) patients who have undergone primary tumor resection.

Methods: The study included 40 consecutive patients with incurable stage IV CRC who underwent primary tumor resection at our hospital between 2011 and 2015. Patients were divided into subgroups of low and high Ang-1, Ang-2, and Tie-2. Patient age and sex, tumor location, TNM stages, vascular invasion, chemotherapy, and overall survival were assessed.

Results: The cut-off values of Ang-1, Ang-2, and Tie-2 were 0.4, 1.8, and 15.0 ng/mL, respectively. Overall survival was significantly longer in the low Ang-2 group than in the high Ang-2 group. High Ang-2 levels were associated with age, N stage, and chemotherapy. Immunofluorescent staining of Ang-2 revealed that endothelial cells and cancer cells expressed Ang-2 in each case.

Conclusions: Our findings suggest that the serum Ang-2 level is associated with disease progression and is an important predictor of mortality in incurable stage IV CRC patients. Thus, it may be a useful prognostic biomarker in these patients.

Keywords: Angiopoietin; Colorectal cancer; Metastasis; Prognosis; Surgery.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Angiopoietin-1 / blood
  • Angiopoietin-2 / blood*
  • Angiopoietin-2 / metabolism
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / metabolism
  • Chemotherapy, Adjuvant
  • Colon / pathology
  • Colon / surgery
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / therapy
  • Endothelial Cells / pathology
  • Feasibility Studies
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Preoperative Period
  • Prognosis
  • Receptor, TIE-2 / blood
  • Rectum / pathology
  • Rectum / surgery
  • Reference Values
  • Risk Assessment / methods
  • Risk Factors


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