title: High circulating hepatocyte growth factor levels associate with epithelial to mesenchymal transition and poor outcome in small cell lung cancer patients.
abstract: 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=0.006) 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 supports testing Met inhibitors in patients with high sHGF.
authors.affiliation: Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Doctor Aiguader, Barcelona; These authors equally contributed to the work.
authors.forename: Israel
authors.initials: I
authors.lastname: Cañadas
authors.affiliation: Servei d'Oncologia Médica, Hospital del Mar, Passeig Marítim, Barcelona; These authors equally contributed to the work.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Taus
authors.affiliation: Servei d'Oncologia Médica, Hospital del Mar, Passeig Marítim, Barcelona.
authors.forename: Iria
authors.initials: I
authors.lastname: González
authors.affiliation: Servei d'Oncologia Médica, Hospital del Mar, Passeig Marítim, Barcelona.
authors.forename: Xavier
authors.initials: X
authors.lastname: Villanueva
authors.affiliation: Servei de Patologia, Hospital del Mar, Passeig Marítim, Barcelona.
authors.forename: Javier
authors.initials: J
authors.lastname: Gimeno
authors.affiliation: Servei de Patologia, Hospital del Mar, Passeig Marítim, Barcelona.
authors.forename: Lara
authors.initials: L
authors.lastname: Pijuan
authors.affiliation: Oncology Department, IIS-Fundación Jiménez Díaz, Avenida Reyes Católicos, Madrid.
authors.forename: Manuel
authors.initials: M
authors.lastname: Dómine
authors.affiliation: Servei de Pneumologia, Hospital del Mar, Passeig Marítim, Barcelona.
authors.forename: Albert
authors.initials: A
authors.lastname: Sánchez-Font
authors.affiliation: Servei de Radiologia, Hospital del Mar, Passeig Marítim, Barcelona.
authors.forename: Ivan
authors.initials: I
authors.lastname: Vollmer
authors.affiliation: Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Doctor Aiguader, Barcelona.
authors.forename: Silvia
authors.initials: S
authors.lastname: Menéndez
authors.affiliation: Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Doctor Aiguader, Barcelona.
authors.forename: Oriol
authors.initials: O
authors.lastname: Arpí
authors.affiliation: Consulting Service on Methodology for Biomedical Research, IMIM, Doctor Aiguader, Barcelona.
authors.forename: Sergi
authors.initials: S
authors.lastname: Mojal
authors.affiliation: Pathology Department, IIS-Fundación Jiménez Díaz, Avenida Reyes Católicos, Madrid.
authors.forename: Federico
authors.initials: F
authors.lastname: Rojo
authors.affiliation: Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Doctor Aiguader, Barcelona; Servei d'Oncologia Médica, Hospital del Mar, Passeig Marítim, Barcelona.
authors.forename: Ana
authors.initials: A
authors.lastname: Rovira
authors.affiliation: Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Doctor Aiguader, Barcelona; Servei d'Oncologia Médica, Hospital del Mar, Passeig Marítim, Barcelona; Pompeu Fabra University, Doctor Aiguader, Barcelona.
authors.forename: Joan
authors.initials: J
authors.lastname: Albanell
authors.affiliation: Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Doctor Aiguader, Barcelona; Servei d'Oncologia Médica, Hospital del Mar, Passeig Marítim, Barcelona.
authors.forename: Edurne
authors.initials: E
authors.lastname: Arriola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D055752:Small Cell Lung Carcinoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor