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

Abstract

<b><i>Background:</i></b> 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. <b><i>Materials and Methods:</i></b> 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, <i>HO-</i>1 mRNA in colorectal cancer was examined by reverse transcription polymerase chain reaction. <b><i>Results:</i></b> 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 (<i>p</i> < 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. <i>HO-1</i> mRNA expression was confirmed in colorectal normal and cancer tissues. <b><i>Conclusion:</i></b> 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.

The Diverse Roles of Heme Oxygenase-1 in Tumor Progression

“…There are several studies supporting the pro-metastatic role of HO-1, where over-expression of the enzyme has correlated with an increase in metastatic potential ( 152 , 161 – 163 ). In human advanced colorectal cancer, HO-1 is correlated to lymph node metastasis and a shorter disease-free survival time ( 164 ). In a loss of function example, pharmacological inhibition of HO-1 activity using SnMP in mice bearing orthotopic 4T1 mammary tumors, despite not controlling growth of the primary tumor, suppressed the number of pulmonary metastasis ( 27 ).…”

Pathological significance of heme oxygenase-1 as a potential tumor promoter in heme-induced colorectal carcinogenesis

“… 58 Recent evidence demonstrates that HMOX1-induced modulation of immune cell communication with the CRC tumor microenvironment is positively associated with lymph node metastasis and poor survival outcomes in advanced stages. 48 , 62 Therefore, HMOX1 induction in the tumor microenvironment facilitates tumor progression through immune evasion and increases chemoresistance.…”

Iron metabolism and chronic inflammation in IgA nephropathy

“…The HO-1 system allows macrophages to protect tissues from oxidative damage, a role that is associated with an important beneficial role in atherosclerosis, ischemic injury and kidney disease [ 197–199 ]. Although HO-1 is broadly anti-inflammatory in nature, it is not always beneficial and is associated with deleterious outcomes in diseases such as cancer, obesity, and chronic infections [ 200–202 ]. Thus, induction or inhibition of HO-1 in macrophages may have therapeutic effects, depending on the disease context.…”