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Updated: Mar 7, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Correlation of c-Met Expression and Outcome in Patients With Renal Cell Carcinoma Treated With Sunitinib
Katriina Johanna Peltola1, Patrick Penttilä1, Juhana Rautiola1
1Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland.
Background:
Treatment of patients with metastatic renal cell carcinoma (mRCC) has improved substantially since the introduction of targeted therapies, but no predictive biomarkers are available. The proto-oncogene c-Met is involved in tumor angiogenesis, development, and metastasis. The main objective was to evaluate c-Met expression in sunitinib-treated patients with mRCC, including patients with bone metastases.
Methods:
c-Met expression was analyzed from 137 formalin-fixed paraffin-embedded tumor samples using a validated immunostaining protocol.
Results:
Patients with low c-Met expression (n = 78) had longer progression-free survival (PFS) (median 14.3 vs. 6.5 months; P < .001) and overall survival (OS) (median 32.1 vs. 20.1 months; P = .049) than those with high expression. High c-Met expression was an independent predictor of unfavorable PFS in a Cox proportional hazards model adjusted for the Heng risk criteria (HR 1.60 [1.09-2.35]; P = .016). In a subgroup of patients with no bone metastases (n = 106), low c-Met expression was associated with a both longer OS (unadjusted HR 0.63 [95% CI, 0.42-0.95]; P = .034) and PFS (unadjusted HR 0.47 [95% CI, 0.31-0.71]; P < .001).
Conclusions:
High c-Met expression was associated with poor survival in patients with mRCC treated with sunitinib. Interestingly, the prognostic role may vary based on the location of metastases.
Insights
Low c-Met expression is linked to better survival in metastatic renal cell carcinoma (mRCC) patients on sunitinib. High c-Met expression predicts worse outcomes, but metastasis location may influence prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Metastatic renal cell carcinoma (mRCC) treatment has advanced with targeted therapies, yet predictive biomarkers remain elusive.
- The proto-oncogene c-Met plays a role in tumor angiogenesis, development, and metastasis.
- Understanding c-Met's role could improve patient stratification and treatment strategies for mRCC.
Purpose of the Study:
- To evaluate c-Met expression as a predictive biomarker in patients with mRCC treated with sunitinib.
- To assess the association between c-Met expression levels and clinical outcomes, including progression-free survival (PFS) and overall survival (OS).
- To investigate the impact of bone metastases on the prognostic value of c-Met expression.
Main Methods:
- Analysis of c-Met expression in 137 formalin-fixed paraffin-embedded tumor samples from mRCC patients.
- Utilized a validated immunostaining protocol for accurate c-Met quantification.
- Statistical analysis, including Cox proportional hazards models, to correlate c-Met expression with survival outcomes, adjusted for Heng risk criteria.
Main Results:
- Patients with low c-Met expression demonstrated significantly longer PFS (14.3 vs. 6.5 months) and OS (32.1 vs. 20.1 months) compared to those with high expression.
- High c-Met expression was an independent predictor of unfavorable PFS (HR 1.60).
- In patients without bone metastases, low c-Met expression was associated with longer OS and PFS.
Conclusions:
- High c-Met expression is associated with poor survival in sunitinib-treated mRCC patients.
- c-Met expression serves as a potential prognostic biomarker for mRCC.
- The prognostic significance of c-Met may be influenced by the presence and location of metastases, particularly bone metastases.
