Overexpression of c-met Protein in Gastric Cancer and Role of uPAR as a Therapeutic Target

Abstract

Purpose: One of the members of the tyrosine kinase receptor family is the protein product of the c-met proto-oncogene, which is the receptor for hepatocyte growth factor (HGF). HGF is known as a potent mitogen and motogen for many kinds of carcinoma cells, and has been found to simulate the growth and progression of gastric cancer cells through HGF-receptors. In addition, the urokinase-type plasminogen activator (uPA) and receptor (uPAR) also play important roles in the invasion and metastasis. Materials and Methods: The expression of c-met protein was investigated using immunohistochemical staining of 50 paraffin embedded gastric cancers, and by measuring the serum uPAR levels, before and after an operation, in gastric cancer patients using an ELISA assay. Results: Of the 50 cases, 32 (64%) expressed the c-met protein. The c-met protein expression was significantly correlated with the TNM staging (p＜0.05), but the other prognostic factors were not significant variables. According to a Kaplan-Meier's plot, the one and three year overall survival rates were 94 and 70% in patients not expressing the c-met protein, and 81 and 33% in those that did, and the Survival curves revealed a significantly different prognosis (p=0.04). Elevated serum uPAR levels (≥3257.8 pg/ml, control mean±2SD) were observed in 9 (34.6%) of 26 gastric cancer patients, but in none of control subjects. Average serum uPAR levels were 2980.8±616.2 pg/ml before the operation and 2404.7±455.9 pg/ml after, and decreased significantly after surgical resection (p＜0.05). The serum uPAR level correlated significantly with lymph node metastasis and vessel invasion (p＜0.05) Conclusion: The expression of c-met protein, and the level of uPAR, may be prognostic factors in gastric cancer. (Cancer Res Treat. 2003;35:9-15)