c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.
c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.
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DOI：
10.1186/s12885-015-1450-3
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发表时间：
2015-06-03
期刊：
影响因子：
3.8
通讯作者：
Sasano H
中科院分区：
文献类型：
--
作者：
Ozawa Y;Nakamura Y;Fujishima F;Felizola SJ;Takeda K;Okamoto H;Ito K;Ishida H;Konno T;Kamei T;Miyata G;Ohuchi N;Sasano H
C-Met在多种人类恶性肿瘤中被认为是一个预后不良的因素。已有研究表明c-Met和/或其配体肝细胞生长因子(HGF)参与了食管鳞癌(ESCC)的发生，但c-Met状态与临床预后的关系尚不清楚。此外，新的分子治疗靶点的确定可能有助于改善ESCC患者的临床结果。采用免疫组织化学方法检测104例手术标本中c-Met和HGF的表达。分析c-Met/HGF的表达与患者生存期等临床病理特征的关系。我们还研究了在HGF和/或c-Met抑制剂处理下，ESCC细胞功能和c-Met及其下游信号通路成分的蛋白表达的变化。C-Met的高表达与肿瘤深度和病理分期显著相关。C-Met高表达患者的生存率明显较差。此外，多因素分析表明c-Met的高表达是独立的预后因素。在HGF刺激下用c-Met抑制剂显著抑制c-Met mRNA表达升高的ESCC细胞株的侵袭能力。此外，经c-Met抑制剂处理后，c-Met及其下游信号转导失活。我们的研究结果证实c-Met的表达是ESCC患者的一个独立的预后因素，并表明c-Met可能成为治疗c-Met表达升高的ESCC的潜在分子治疗靶点。本文的在线版本(doi：10.1186/s12885-0151450-3)包含补充材料，授权用户可以使用。
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. 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. 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. 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. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users.
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DOI：
10.1158/1078-0432.ccr-08-3252
发表时间：
2009-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Knowles LM;Stabile LP;Egloff AM;Rothstein ME;Thomas SM;Gubish CT;Lerner EC;Seethala RR;Suzuki S;Quesnelle KM;Morgan S;Ferris RL;Grandis JR;Siegfried JM
通讯作者：
Siegfried JM
影响因子：
--
作者：
Kawakami H;Okamoto I;Arao T;Okamoto W;Matsumoto K;Taniguchi H;Kuwata K;Yamaguchi H;Nishio K;Nakagawa K;Yamada Y
通讯作者：
Yamada Y
影响因子：
2.8
作者：
Lau, Patrick C.;Wong, Elaine Y.
通讯作者：
Wong, Elaine Y.
影响因子：
20.4
作者：
Onozato, Ryoichi;Kosaka, Takayuki;Mitsudomi, Tetsuya
通讯作者：
Mitsudomi, Tetsuya
影响因子：
9.7
作者：
Kammula, Udal S.;Kuntz, Eleanor J.;Weiser, Martin R.
通讯作者：
Weiser, Martin R.