Clinical Research Papers:
High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients
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Israel Cañadas1,*, Álvaro Taus2,*, Iria González2, Xavier Villanueva2, Javier Gimeno3, Lara Pijuan3, Manuel Dómine4, Albert Sánchez-Font5, Ivan Vollmer6, Silvia Menéndez1, Oriol Arpí1, Sergi Mojal7, Federico Rojo8, Ana Rovira1,2, Joan Albanell1,2,9 and Edurne Arriola1,2
1. Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Doctor Aiguader, Barcelona
2. Servei d’Oncologia Médica, Hospital del Mar, Passeig Marítim, Barcelona
3. Servei de Patologia, Hospital del Mar, Passeig Marítim, Barcelona
4. Oncology Department, IIS-Fundación Jiménez Díaz, Avenida Reyes Católicos, Madrid
5. Servei de Pneumologia, Hospital del Mar, Passeig Marítim, Barcelona
6. Servei de Radiologia, Hospital del Mar, Passeig Marítim, Barcelona
7. Consulting Service on Methodology for Biomedical Research, IMIM, Doctor Aiguader, Barcelona
8. Pathology Department, IIS-Fundación Jiménez Díaz, Avenida Reyes Católicos, Madrid
9. Pompeu Fabra University, Doctor Aiguader, Barcelona
* These authors equally contributed to the work
Edurne Arriola, email:
Keywords: Small Cell Lung Cancer, Hepatocyte Growth Factor, Met, Epithelial to Mesenchymal Transition, Chemoresistance
Received: May 14, 2014 Accepted: June 18, 2014 Published: June 20, 2014
We have previously shown that Met activation through the hepatocyte growth factor (HGF) increases tumorogenesis, induces epithelial-to-mesenchymal transition (EMT) and chemoresistance in SCLC. We sought to evaluate circulating HGF levels in SCLC patients and assess correlation with outcome and EMT features in the tumor. Serum samples from patients with SCLC were prospectively obtained at diagnosis, response evaluation and progression. HGF serum (sHGF) was quantified by ELISA. EMT markers and p-Met/Met were assayed by immunohistochemistry in tumor samples. Clinical data were prospectively recorder. One-hundred twelve patients were included. High baseline levels of sHGF were associated with shorter overall survival (p=0.007) and remained independently associated with survival in the multivariate analysis (p=0.016). For stage IV patients, an increase of sHGF levels at response evaluation (p=0.042) and at progression (p=0.003) were associated with poor outcome. sHGF levels were associated (p<0.05) with a mesenchymal phenotype in the tumor. In conclusion, high sHGF at diagnosis and increases during the course of the disease predict for poor outcome in SCLC patients and associate with EMT in the tumor. These data provide novel evidence on a role of sHGF in the adverse clinical behavior of SCLC and support testing Met inhibitors in patients with high sHGF.
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