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



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.


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.


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.


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.

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Receiver operating characteristic




Colorectal cancer


Performance status


American Society of Anesthesiologists


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This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science Wakate Grant 16K09821 and 19K18104 (to S.M.)

Author information




Study concept and design: S.M. Data acquisition: S.M., T.U., H.I., H.K., R.T., M.K., M.T., Y.K., Y.T., K.S. Analysis and interpretation of data: S.M. Drafting of the manuscript: S.M. Critical revision of the manuscript: S.M.

Corresponding author

Correspondence to Shinya Munakata.

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The authors declare no conflict of interest.

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This study was performed in accordance with the ethical standards of the Committee on Human Experimentation of our institution. All procedures were followed in accordance with the current revision of Helsinki Declaration.

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Munakata, S., Ueyama, T., Ishihara, H. et al. Angiopoietin-2 as a Prognostic Factor in Patients with Incurable Stage IV Colorectal Cancer. J Gastrointest Canc 52, 237–242 (2021).

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  • Colorectal cancer
  • Angiopoietin
  • Surgery
  • Prognosis
  • Metastasis