TY - JOUR
T1 - c-Met in esophageal squamous cell carcinoma
T2 - An independent prognostic factor and potential therapeutic target
AU - Ozawa, Yohei
AU - Nakamura, Yasuhiro
AU - Fujishima, Fumiyoshi
AU - Felizola, Saulo J.A.
AU - Takeda, Kenichiro
AU - Okamoto, Hiroshi
AU - Ito, Ken
AU - Ishida, Hirotaka
AU - Konno, Takuro
AU - Kamei, Takashi
AU - Miyata, Go
AU - Ohuchi, Noriaki
AU - Sasano, Hironobu
N1 - Funding Information:
This study was supported by a research funding from Department of Pathology and Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine. We appreciate the skillful technical assistance of Ms. Kazue Ise (Department of Pathology, Tohoku University Graduate School of Medicine) and Ms. Yasuko Furukawa (Division of Advanced Surgical Science and Technology, Tohoku University Graduate School of Medicine). We would like to thank Editage (www.editage.jp) for English language review.
Publisher Copyright:
© 2015 Ozawa et al.
PY - 2015/6/3
Y1 - 2015/6/3
N2 - 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.
AB - 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.
KW - Esophageal squamous cell carcinoma
KW - Hepatocyte growth factor
KW - Immunohistochemistry
KW - Molecular targeted therapy
KW - c-Met
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U2 - 10.1186/s12885-015-1450-3
DO - 10.1186/s12885-015-1450-3
M3 - Article
C2 - 26036285
AN - SCOPUS:84930616492
SN - 1471-2407
VL - 15
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 451
ER -
