Abstract | BACKGROUND: c-N-Methyl-N'-nitro-N-nitroso- guanidine HOS transforming gene (c-MET) is a new potential drug target for treatment of patients with hepatocellular carcinoma (HCC), and a recent study of a c-MET inhibitor in such patients has shown promising results. In the present study, we investigated the incidence of c-MET overexpression and its prognostic impact. MATERIALS AND METHODS:
Tumor tissue microarrays were used to detect the expression of c-MET in samples from 287 patients with HCC who underwent surgical resection at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features of HCC, and investigated recurrence-free survival (RFS) and HCC-specific survival according to the level of c-MET expression. Additionally, we explored the correlation between c-MET protein overexpression, and MET mRNA expression and copy number variation. RESULTS: Most patients in the present study were male (n=297, 82.6%), with Child-Pugh class A liver function (n=286, 99.7%) and hepatitis B viral infection (n=217, 75.6%). c-MET overexpression was observed in 80 patients (27.9%), and was not associated with Edmondson grade, tumor size, microvascular invasion, major portal vein invasion or stage. In addition, c-MET expression levels did not affect RFS or HCC-specific survival. c-MET expression was weakly correlated with c-MET copy number variation (r=0.255, p<0.001), but more than half of all patients with c-MET overexpression had a neutral c-MET copy number. c-MET protein expression was very weakly but significantly positively correlated with its mRNA expression (r=0.199, p=0.002). CONCLUSION: c-MET overexpression did not have any prognostic impact on recurrence or survival of patients with HCC undergoing surgical resection. However, 27.9% of patients who had c-MET overexpression could be considered candidates for treatment with c-MET inhibitor.
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Authors | Su Jin Lee, Jeeyun Lee, Insuk Sohn, Mao Mao, Wang Kai, Cheol-Keun Park, Ho Yeong Lim |
Journal | Anticancer research
(Anticancer Res)
Vol. 33
Issue 11
Pg. 5179-86
(Nov 2013)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 24222167
(Publication Type: Journal Article)
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Chemical References |
- Biomarkers, Tumor
- RNA, Messenger
- MET protein, human
- Proto-Oncogene Proteins c-met
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Topics |
- Adolescent
- Adult
- Aged
- Biomarkers, Tumor
(analysis)
- Carcinoma, Hepatocellular
(genetics, metabolism, mortality, surgery)
- DNA Copy Number Variations
- Female
- Follow-Up Studies
- Gene Amplification
- Humans
- Immunoenzyme Techniques
- Liver Neoplasms
(genetics, metabolism, mortality, surgery)
- Male
- Middle Aged
- Neoplasm Recurrence, Local
(genetics, metabolism, mortality, surgery)
- Neoplasm Staging
- Prognosis
- Proto-Oncogene Proteins c-met
(genetics, metabolism)
- RNA, Messenger
(genetics)
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Survival Rate
- Young Adult
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