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High expression of heme oxygenase-1 is associated with tumor invasiveness and poor clinical outcome in non-small cell lung cancer patients

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Abstract

Background

Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, is known to play a role in the protection of cells against oxidative stress, inflammation, anomalous proliferation and apoptosis. As yet, the role of HO-1 expression in non-small cell lung cancer (NSCLC) development and metastasis remains unclear and insufficient data are available regarding its impact on the prognosis of NSCLC patients.

Methods

Seventy NSCLC patients who underwent surgical resection were included in this HO-1 expression study and, concomitantly, clinical parameters were collected. Two lung adenocarcinoma cell lines (A549 and H441) were used to assess both invasive and migratory parameters in vitro.

Results

NSCLC patients with a high HO-1 expression ratio (tumor tissue/normal tissue) (> 1) exhibited a significantly poorer prognosis and a higher metastatic rate compared to those with a low HO-1 expression ratio (p < 0.05). The invasive and migratory abilities of A549 and H441 cells significantly increased after exogenous HO-1 over-expression and significantly decreased after siRNA-mediated HO-1 expression silencing. HO-1 up- and down-regulation also positively correlated with the expression of metastasis-associated proteins EGFR, CD147 and MMP-9. In addition, we found that HO-1 expression can be inhibited by PI3K and AKT inhibitors, but not by MAPK inhibitors.

Conclusions

HO-1 is a poor prognostic NSCLC predictor and its over-expression may increase the metastatic potential of NSCLC. Based on our findings and those of others, HO-1 may be considered as a novel NSCLC therapeutic target.

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Acknowledgements

This study was supported by grants from the National Science Council, grants NSC NSC99-2314-B-037-058-MY2 and NSC 100-2320-B-039-008-MY2, Kaohsiung Medical University Hospital grant KMUH99-9 M64, and Kaohsiung Medical University grant KMU-Q098022, Taiwan.

Disclosure/state of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Jong-Rung Tsai, Po-Len Liu, Shah-Hwa Chou, Jhi-Jhu Hwang & Inn-Wen Chong

  2. Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Jong-Rung Tsai, Jhi-Jhu Hwang & Inn-Wen Chong

  3. Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hui-Min Wang

  4. Graduate Institute of Integrated Medicine, College of Chinese Medicine, Department of Urology, China Medical University and Hospital, Taichung, Taiwan

    Yung-Hsiang Chen

  5. Department of Surgery, Yuan’s General Hospital, Kaohsiung, Taiwan

    Ming-Chan Yang

  6. Department of Surgery, Division of Chest Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Shah-Hwa Chou

  7. Department of Health Management, Division of Thoracic Surgery, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

    Yu-Jen Cheng

  8. Division of Cardiology, Cheng-Hsin General Hospital, Faculty of Medicine, and Cardiovascular Research Centre, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Wei-Hsian Yin

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  1. Jong-Rung Tsai
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  2. Hui-Min Wang
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Correspondence to Jhi-Jhu Hwang or Inn-Wen Chong.

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Tsai, JR., Wang, HM., Liu, PL. et al. High expression of heme oxygenase-1 is associated with tumor invasiveness and poor clinical outcome in non-small cell lung cancer patients. Cell Oncol. 35, 461–471 (2012). https://doi.org/10.1007/s13402-012-0105-5

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