c-Met in esophageal squamous cell carcinoma: An independent prognostic factor and potential therapeutic target

Yohei Ozawa, Yasuhiro Nakamura, Fumiyoshi Fujishima, Saulo J.A. Felizola, Kenichiro Takeda, Hiroshi Okamoto, Ken Ito, Hirotaka Ishida, Takuro Konno, Takashi Kamei, Go Miyata, Noriaki Ohuchi, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. Methods: The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Results: Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. Conclusions: The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

Original languageEnglish
Article number451
JournalBMC Cancer
Volume15
Issue number1
DOIs
Publication statusPublished - 2015 Jun 3

Keywords

  • Esophageal squamous cell carcinoma
  • Hepatocyte growth factor
  • Immunohistochemistry
  • Molecular targeted therapy
  • c-Met

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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