Molecular co-expression of the c-Met oncogene and hepatocyte growth factor in primary colon cancer predicts tumor stage and clinical outcome Journal Article
| Authors: | Kammula, U. S.; Kuntz, E. J.; Francone, T. D.; Zeng, Z.; Shia, J.; Landmann, R. G.; Paty, P. B.; Weiser, M. R. |
| Article Title: | Molecular co-expression of the c-Met oncogene and hepatocyte growth factor in primary colon cancer predicts tumor stage and clinical outcome |
| Abstract: | 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 over-expression 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. © 2006 Elsevier Ireland Ltd. All rights reserved. |
| Keywords: | survival; adult; cancer survival; controlled study; human tissue; protein expression; aged; middle aged; survival analysis; survival rate; human cell; major clinical study; clinical feature; cancer patient; cancer staging; neoplasm staging; adenocarcinoma; protein analysis; phenotype; metastasis; gene expression; tumor markers, biological; colonic neoplasms; scatter factor; correlation analysis; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; colon cancer; outcome; tumor growth; colon adenocarcinoma; scatter factor receptor; tumor stage; tumor progression; proto-oncogene proteins c-met; c-met; hepatocyte growth factor; hgf |
| Journal Title: | Cancer Letters |
| Volume: | 248 |
| Issue: | 2 |
| ISSN: | 0304-3835 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 2007-04-18 |
| Start Page: | 219 |
| End Page: | 228 |
| Language: | English |
| DOI: | 10.1016/j.canlet.2006.07.007 |
| PUBMED: | 16945480 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 39" - "Export Date: 17 November 2011" - "CODEN: CALED" - "Source: Scopus" |
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