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A survey of c-MET expression and amplification in 287 patients with hepatocellular carcinoma
Su Jin Lee1, Jeeyun Lee, Insuk Sohn
1Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea. Tel: +82 234102766 ckpark@skku.edu.
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.
Insights
c-MET overexpression was found in 27.9% of hepatocellular carcinoma patients but did not impact survival. These patients may benefit from c-MET inhibitor therapy.
Area of Science:
- Oncology
- Hepatocellular Carcinoma Research
- Molecular Biology
Background:
- The c-N-Methyl-N'-nitro-N-nitroso-guanidine HOS transforming gene (c-MET) is a potential therapeutic target for hepatocellular carcinoma (HCC).
- Recent studies show promise for c-MET inhibitors in HCC treatment.
- Investigating c-MET overexpression and its prognostic significance is crucial.
Purpose of the Study:
- To determine the incidence of c-MET overexpression in HCC patients undergoing surgical resection.
- To evaluate the prognostic impact of c-MET overexpression on recurrence-free survival (RFS) and HCC-specific survival.
- To explore correlations between c-MET protein expression, mRNA levels, and copy number variations.
Main Methods:
- Analysis of tumor tissue microarrays from 287 HCC patients.
- Assessment of c-MET expression levels and correlation with clinicopathological features.
- Investigation of RFS and HCC-specific survival based on c-MET expression levels.
- Exploration of the relationship between protein expression, mRNA levels, and copy number variations.
Main Results:
- c-MET overexpression was detected in 27.9% of HCC patients.
- c-MET overexpression was not associated with key clinicopathological features like tumor grade, size, or invasion.
- c-MET expression levels did not significantly affect RFS or HCC-specific survival.
- Weak correlations were observed between c-MET protein expression and its mRNA levels and copy number variations.
Conclusions:
- c-MET overexpression in HCC does not appear to influence patient prognosis regarding recurrence or survival after surgical resection.
- A significant proportion of HCC patients (27.9%) exhibit c-MET overexpression, identifying them as potential candidates for c-MET inhibitor therapies.
