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Soluble c-Met in serum of patients with multiple myeloma: correlation with clinical parameters
Karin F Wader1, Unn-Merete Fagerli, Randi U Holt
1Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim. karin.f.wader@ntnu.no
Objectives:
The receptor tyrosine kinase c-Met and its ligand, hepatocyte growth factor (HGF), play key roles in tumour genesis and metastasis and contribute in multiple myeloma pathogenesis. Substantial data support that a soluble extracellular fragment of c-Met may function as a decoy receptor that downregulates the biological effects of HGF and c-Met. We examined serum levels of soluble c-Met in patients with myeloma and healthy individuals and investigated a possible relationship with clinical disease parameters and survival.
Methods:
The concentration of c-Met and HGF was measured by enzyme-linked immunosorbent assay in serum (n=49) and bone marrow plasma (n=16) from patients with multiple myeloma and in serum from healthy controls (n=26).
Results:
The median serum concentration of soluble c-Met was 186 ng/mL (range 22-562) in patients with multiple myeloma and 189 ng/mL (range 124-397) in healthy individuals. There was a significant negative correlation between serum c-Met levels and disease stage, bone marrow plasma cell percentage and serum concentration of M-protein.
Conclusion:
We have for the first time examined the concentration of soluble c-Met in serum from patients with myeloma and found equal median levels in patients with myeloma as a group and healthy individuals. Still, serum levels of soluble c-Met correlated negatively with parameters of disease burden in patients with myeloma. We suggest that a possible role for the c-Met ectodomain as a negative regulator of HGF/c-Met activity should be examined in multiple myeloma.
Insights
Serum levels of soluble c-Met were similar in multiple myeloma patients and healthy individuals. However, lower soluble c-Met correlated with higher disease burden, suggesting a regulatory role in myeloma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), are implicated in multiple myeloma pathogenesis, tumor genesis, and metastasis.
- A soluble extracellular fragment of c-Met may act as a decoy receptor, potentially downregulating HGF/c-Met signaling.
- Understanding the role of soluble c-Met in multiple myeloma is crucial for exploring novel therapeutic strategies.
Purpose of the Study:
- To examine serum levels of soluble c-Met in patients with multiple myeloma compared to healthy individuals.
- To investigate the relationship between serum soluble c-Met concentrations and clinical disease parameters, including disease stage, M-protein levels, and bone marrow plasma cell percentage.
- To explore the potential correlation between soluble c-Met levels and survival in multiple myeloma patients.
Main Methods:
- Serum and bone marrow plasma samples were collected from multiple myeloma patients (n=49) and healthy controls (n=26).
- Concentrations of soluble c-Met and HGF were quantified using enzyme-linked immunosorbent assay (ELISA).
- Statistical analysis was performed to compare levels and identify correlations with clinical parameters.
Main Results:
- Median serum concentrations of soluble c-Met were comparable between multiple myeloma patients (186 ng/mL) and healthy individuals (189 ng/mL).
- A significant negative correlation was observed between serum soluble c-Met levels and indicators of disease burden, including disease stage, bone marrow plasma cell percentage, and serum M-protein concentration.
- No significant correlation was found between serum c-Met levels and survival in this cohort.
Conclusions:
- This study is the first to report comparable serum levels of soluble c-Met in multiple myeloma patients and healthy individuals.
- Despite similar overall levels, serum soluble c-Met concentrations negatively correlate with disease burden in multiple myeloma.
- Further research is warranted to elucidate the potential role of the c-Met ectodomain as a negative regulator of HGF/c-Met activity in multiple myeloma.
