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Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder
1Department of Urology, National Cheng Kung University, 1 Ta-Hsueh Road, Tainan 70428, Taiwan.
Abstract:
Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c-met proto-oncogene family. We examined the mutational and expression patterns of RON in eight human uroepithelial cell lines. Biological effects of RON overexpression on cancer cells were investigated in vitro, and the prognostic significance of RON and/or c-met protein (MET) expression was analysed in a bladder cancer cohort (n=183). There was no evidence of mutation in the kinase domain of RON. Overexpression of RON using an inducible Tet-off system induced increased cell proliferation, motility, and antiapoptosis. Immunohistochemical analysis showed that RON was overexpressed in 60 cases (32.8%) of primary tumours, with 14 (23.3%) showing a high level of expression. Recepteur d'Origine Nantais expression was positively associated with histological grading, larger size, nonpapillary contour, and tumour stage (all P<0.01). In addition, MET was overexpressed in 82 cases (44.8%). Co-expressed RON and MET was significantly associated with decreased overall survival (P=0.005) or metastasis-free survival (P=0.01) in 35 cases (19.1%). Recepteur d'Origine Nantais-associated signalling may play an important role in the progression of human bladder cancer. Evaluation of RON and MET expression status may identify a subset of bladder-cancer patients who require more intensive treatment.
Insights
Receptor tyrosine kinase RON overexpression in bladder cancer correlates with advanced disease. Co-expression of RON and c-met (MET) predicts poorer survival, suggesting their potential as therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Receptor tyrosine kinases (RTKs) play crucial roles in cell signaling.
- The c-met proto-oncogene family includes RON, a distinct RTK implicated in cancer progression.
- Dysregulation of RTKs like RON and MET is frequently observed in various human malignancies.
Purpose of the Study:
- To investigate the mutational and expression patterns of Receptor d'Origine Nantais (RON) in human uroepithelial cells.
- To determine the biological effects of RON overexpression on cancer cells in vitro.
- To analyze the prognostic significance of RON and c-met (MET) protein expression in bladder cancer.
Main Methods:
- Analysis of RON mutational and expression patterns in eight human uroepithelial cell lines.
- In vitro studies of RON overexpression effects using an inducible Tet-off system.
- Immunohistochemical analysis of RON and MET expression in a bladder cancer cohort (n=183).
Main Results:
- No mutations were found in the kinase domain of RON.
- RON overexpression increased cell proliferation, motility, and anti-apoptosis.
- RON was overexpressed in 32.8% of primary bladder tumors and associated with higher grade, larger size, non-papillary contour, and advanced stage.
- MET was overexpressed in 44.8% of tumors.
- Co-expression of RON and MET significantly correlated with decreased overall survival and metastasis-free survival.
Conclusions:
- Receptor d'Origine Nantais signaling is implicated in human bladder cancer progression.
- RON overexpression is linked to aggressive tumor characteristics.
- Combined evaluation of RON and MET expression may identify bladder cancer patients needing intensified treatment.