Heme oxygenase-1 expression is associated with tumor aggressiveness and outcomes in patients with bladder cancer: a correlation with smoking intensity.

Abstract

Heme oxygenase (HO)-1 is upregulated in malignancies and, in turn, regulates other cancer-related factors. Although HO-1 expression has been associated with cigarette smoking under various pathologic conditions, little is known about their association in patients with bladder cancer. HO-1 expression was assessed in 215 formalin-fixed bladder cancer specimens by immunohistochemistry. Microvessel density, lymph vessel density (LVD), proliferation index (PI), and expression of the vascular endothelial growth factor (VEGF)-A, -C, and -D, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, and MMP-9 were investigated by similar methods. Multivariate analyses were performed to evaluate the pathologic role and predictive value of HO-1 expression. Our results demonstrated that HO-1 expression was positively associated with T stage, lymph node metastasis, and grade. HO-1 expression was also positively correlated with PI, LVD, and expression levels of VEGF-D, COX-2, MMP-2, and MMP-9 (P < 0.001). In addition, multivariate analyses showed that HO-1 expression positively correlated with smoking intensity. Positive HO-1 expression was a significant predictor of subsequent metastasis (P = 0.008) and poor cause-specific survival (P < 0.001). Similarly, multivariate analyses showed that HO-1 expression was a predictor of cause-specific survival (hazard ratio = 3.13, P = 0.013). In conclusion, pathologic changes of HO-1-related factors were dependent on smoking intensity. Smoking upregulated HO-1 expression, and HO-1 was associated with malignant behavior of bladder cancer. Cancer cell proliferation, lymphangiogenesis, and expression levels of VEGF-D, COX-2, and MMP-2 played important roles in these HO-1-related effects. The clinical correlations of HO-1 were regulated by a complex mechanism that depended on smoking intensity.

• Authors: Yasuyoshi Miyata, Shigeru Kanda, Kensuke Mitsunari, Akihiro Asai, Hideki Sakai
• Journal: Translational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 164 Issue 6 Pg. 468-76 (Dec 2014) ISSN: 1878-1810 [Electronic] United States
• PMID: 25063314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Heme Oxygenase-1

Topics

• Aged
• Female
• Heme Oxygenase-1 (metabolism)
• Humans
• Male
• Multivariate Analysis
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Smoking (adverse effects)
• Survival Analysis
• Treatment Outcome
• Urinary Bladder Neoplasms (enzymology, pathology)