Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer

Digestion. 2020;101(4):401-410. doi: 10.1159/000500225. Epub 2019 May 21.


Background: Many cancers express heme oxygenase-1 -(HO-1) at a higher frequency than healthy tissues, and this elevated expression is associated with cancer prognosis. Here, we aim to clarify the correlation between HO-1-expressing macrophage numbers and clinicopathological parameters of advanced colorectal cancer.

Materials and methods: Formalin-fixed and paraffin-embedded tissues of patients with advanced colorectal cancer were used. To detect HO-1 expression in macrophages, immunohistochemistry was performed. The number of positive cells was measured. Furthermore, HO-1 mRNA in colorectal cancer was examined by reverse transcription polymerase chain reaction.

Results: Among the HO-1-negative and HO-1-positive groups, 58.02 and 85.00% of cases, respectively, were positive for lymph node metastasis. The disease-free survival (DFS) time was significantly shorter (p < 0.05) in the -HO-1-positive group (2.44 years) than in the HO-1-negative group (4.09 years). However, according to the Cox proportional-hazards regression model, the HO-1-positive group could not be a risk factor of poor prognosis. HO-1 mRNA expression was confirmed in colorectal normal and cancer tissues.

Conclusion: In this study, the correlation between HO-1-expressing macrophages and clinicopathological parameters in the tumor microenvironment of colorectal cancer was studied for the first time, and the expression was associated with lymph node metastasis and shortening of DFS.

Keywords: Colorectal cancer; Heme oxygenase-1; Immunohistochemistry; Macrophage; Prognosis.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Tumor Microenvironment / genetics*


  • Biomarkers, Tumor
  • RNA, Messenger
  • HMOX1 protein, human
  • Heme Oxygenase-1