Cheng H-L et al. (2005) Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. Br J Cancer 92: 1906–1914

Protein tyrosine kinases are vital to many cell regulatory processes. The majority of known PROTO-ONCOGENES expressed in solid tumors encode protein tyrosine kinases. Understanding their expression patterns could aid cancer prognosis and treatment. Cheng and co-workers have found a link between decreased survival in bladder cancer patients and expression of the receptor tyrosine kinase RON, the c-met protein (MET), or both.

The group studied the biologic effects of RON overexpression in vitro, and retrospectively analyzed RON and MET expression in 183 bladder cancer patients. RON was found to have a significant effect on cell patterns, increasing proliferation, motility, and antiapoptosis of cells. In addition, histologic grade, larger tumor size, and nonpapillary contour were positively associated with RON and MET expression. RON overexpression was also associated with tumor stage, and increased MET levels with muscle invasion (all P <0.01). RON and MET were overexpressed in 32.8% and 44.8% of tumors, respectively; their co-expression led to significantly decreased overall or metastasis-free survival in 35 cases (19.1%) (P = 0.005 and P = 0.01, respectively). Overexpression of MET alone was also associated with poor patient survival (P = 0.06).

The authors conclude that RON-associated signaling might be highly significant in the progression of bladder carcinogenesis. Patients in need of more intensive therapy might be identified by the evaluation of MET and RON expression.