SMO expression level correlates with overall survival in patients with malignant pleural mesothelioma
- Equal contributors
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
Journal of Experimental & Clinical Cancer Research 2013, 32:7 doi:10.1186/1756-9966-32-7Published: 5 February 2013
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.
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.
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.
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.