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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.
AuthorsIsrael Cañadas, Alvaro Taus, Iria González, Xavier Villanueva, Javier Gimeno, Lara Pijuan, Manuel Dómine, Albert Sánchez-Font, Ivan Vollmer, Silvia Menéndez, Oriol Arpí, Sergi Mojal, Federico Rojo, Ana Rovira, Joan Albanell, Edurne Arriola
JournalOncotarget (Oncotarget) Vol. 5 Issue 14 Pg. 5246-56 (Jul 30 2014) ISSN: 1949-2553 [Electronic] United States
PMID25026301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • HGF protein, human
  • Hepatocyte Growth Factor
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Epithelial-Mesenchymal Transition
  • Female
  • Hepatocyte Growth Factor (blood)
  • Humans
  • Lung Neoplasms (blood, drug therapy, pathology)
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Small Cell Lung Carcinoma (blood, drug therapy, pathology)
  • Treatment Outcome

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