Molecular co-expression of the c-Met oncogene and hepatocyte growth factor in primary colon cancer predicts tumor stage and clinical outcome
Molecular co-expression of the c-Met oncogene and hepatocyte growth factor in primary colon cancer predicts tumor stage and clinical outcome
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DOI：
10.1016/j.canlet.2006.07.007
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发表时间：
2007-04-18
期刊：
影响因子：
9.7
通讯作者：
Weiser, Martin R.
中科院分区：
文献类型：
--
作者：
Kammula, Udal S.;Kuntz, Eleanor J.;Weiser, Martin R.
引言/假设：c-Met受体酪氨酸激酶的过表达已在多种癌症中描述并与肿瘤进展有关。与一些实体瘤不同，目前的证据表明，结肠癌中的c-Met激活与基因突变无关，是配体依赖性的，并通过旁分泌方式发生。我们推测，过度表达的c-Met受体及其配体，肝细胞生长因子（HGF）在肿瘤微环境与肿瘤的进展和transferation.Methods：原发性肿瘤c-Met和HGF mRNA的表达进行了分析，在60结肠腺癌。受体和配体的表达进行了分析，与临床病理特征和outcome.Results相关性和关联：与邻近的正常粘膜相比，69%和48%的肿瘤表现出大于2-和大于10倍的c-Met mRNA的升高，分别。在47%的肿瘤中观察到HGF mRNA升高，其中19%的肿瘤增加超过10倍。肿瘤c-Met表达与HGF表达相关，33例患者的队列可以定义为c-Met和HGF表达均低。与27例c-Met或HGF高表达的肿瘤相比，c-Met和HGF低表达的队列具有较少的淋巴结和远处转移以及改善的总生存率（HR = 2.3，p < 0.05）。c-Met和HGF在肿瘤微环境中的共表达可用于结肠癌的分子分期和可行的治疗靶点。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Introduction/hypothesis: Over-expression of the c-Met receptor tyrosine kinase has been described in a variety of cancers and implicated in tumor progression. Unlike some solid tumors, current evidence indicates that c-Met activation in colon cancer is unrelated to gene mutation, is ligand dependent, and occurs via a paracrine fashion. We hypothesize that overexpression of the c-Met receptor and its ligand, hepatocyte growth factor (HGF) in the tumor microenvironment is associated with tumor progression and metastases.Methods: Primary tumor c-Met and HGF mRNA expression was analyzed in 60 colon adenocarcinomas. Receptor and ligand expression was analyzed for correlation and association with clinicopathologic features and outcome.Results: Compared to adjacent normal mucosa, 69% and 48% of tumors showed a greater than 2- and greater than 10-fold elevation in c-Met mRNA, respectively. Elevated HGF mRNA was noted in 47% of tumors with 19% having a greater than 10-fold increase. Tumor c-Met expression was correlated with HGF expression, and a cohort of 33 patients could be defined with both low c-Met and HGF expression. Compared with the 27 tumors with either high c-Met or HGF, the cohort with low c-Met and HGF expression had fewer nodal and distant metastases as well as improved overall survival (HR = 2.3, p < 0.05).Conclusion: Evaluation of the c-Met receptor in context of ligand, HGF, allows identification of a metastatic phenotype that correlates with advanced stage and poor survival. c-Met and HGF co-expression in the tumor microenvironment could be useful in the molecular staging of colon cancer and viable therapeutic targets. (c) 2006 Elsevier Ireland Ltd. All rights reserved.