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Open Access Highly Accessed Research

SMO expression level correlates with overall survival in patients with malignant pleural mesothelioma

Yi Zhang1, Jianxing He2, Fang Zhang3, Hui Li4, Dongsheng Yue45, Changli Wang5, David M Jablons4, Biao He4* and Natalie Lui4*

Author Affiliations

1 Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, 100053, Beijing, China

2 Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, State Key Laboratory of Respiratory Disease, Guangzhou, China

3 Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 314006, Jiaxing, Zhejiang, China

4 Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehen-sive Cancer Center, University of California, 94143, San Francisco, CA, USA

5 Department of Lung Cancer, Tianjin Medical University Cancer Institute & Hospital, 300060, Tianjin, China

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Journal of Experimental & Clinical Cancer Research 2013, 32:7  doi:10.1186/1756-9966-32-7

Published: 5 February 2013

Abstract

Background

Malignant mesothelioma is an aggressive, treatment-resistant tumor arising from mesothelium of pleura, peritoneum and pericardium. Despite current combined regimen, its prognosis remains dismal, calling for more effective targeted therapies. We investigated whether aberrant Hh activation may play a role in mesothelioma.

Methods

SMO and SHH expression levels were analyzed in 46 mesothelioma tissue specimens with real-time RT-PCR, and correlation with survival was analyzed with univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival curves, and the log-rank test. We also examined multiple mesothelioma cell lines for SMO expression and the effect of Hh inhibition by a specific SMO antagonist on cell proliferation by MTS assay.

Results

We observed strong correlation between higher SMO and SHH expression levels with poorer overall survival. Remarkably, Hh inhibition by a specific SMO inhibitor significantly suppressed cell proliferation in the mesothelioma cell lines examined.

Conclusion

Our data strongly support that Hh signaling deregulation plays critical roles in proliferation of mesothelioma, and consistently exerts significant impact on prognosis of the disease. Therefore our findings revealed the hitherto unappreciated role of Hh activation in mesothelioma, and pinpointed Hh signaling antagonist as a potential new therapy against this devastating disease.

Keywords:
Mesothelioma; Hedgehog signaling; Prognosis; Proliferation suppression