Published in:
Open Access
01-12-2015 | Research article
c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target
Authors:
Yohei Ozawa, Yasuhiro Nakamura, Fumiyoshi Fujishima, Saulo JA Felizola, Kenichiro Takeda, Hiroshi Okamoto, Ken Ito, Hirotaka Ishida, Takuro Konno, Takashi Kamei, Go Miyata, Noriaki Ohuchi, Hironobu Sasano
Published in:
BMC Cancer
|
Issue 1/2015
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Abstract
Background
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.