Abstract
PURPOSE: The purpose of this study is to elucidate an increased expression of angiogenin (ANG) as a prognostic factor of gastric cancer (GC), against the background of our previous observations of the increased expression of ANG in the more progressed GC. METHODS: We investigated serum ANG concentrations in 123 GC patients and 63 healthy volunteers as well as the distributions of ANG gene message in 52 GC tissues by in situ hybridization. The prognostic significance of ANG was investigated by the Cox proportional hazards model including variable selection and by survival analysis. RESULTS: The mean serum ANG concentrations in GC patients (378.3+/-95.5 ng/ml) were significantly higher (P=0.0001) than those in the healthy volunteers (334.1+/-58.2 ng/ml). Either strong, moderate, weak, or no ANG gene message expression was seen in 25, 22, 4, and 1 patients, respectively, in GC cells as well as in interstitial cells in the vicinity of cancer cells, a finding in accord with our previous results of ANG protein localization. The variable selection method selected increased (> or =400 ng/ml) serum ANG concentration (P=0.02), undifferentiated histological type (P=0.01), cancer depth (P=0.001), and third-tier lymph node involvement (P=0.0005) as an independent prognostic factor by the Cox proportional hazards model. A significant correlation was seen between higher serum ANG concentrations (> or =400 ng/ml) and worse disease-free (P=0.003) or disease-specific (P=0.03) survivals. CONCLUSIONS. These results suggest that serum levels of ANG are an independent prognostic factor that could be a predictor of postoperative outcomes of GC patients.