An abnormally high expression of ISL-1 represents a potential prognostic factor in gastric cancer

Insulin gene enhancer binding protein-1 (ISL-1) is a transcription factor involved in development of the heart, motor neurons, and pancreas. Our previous study indicated that ISL-1 was overexpressed in gastric cancer but not in other gastrointestinal tumors. However, no immunohistochemical or clinicopathological studies of ISL-1 in gastric carcinoma have been performed. The aim of this study was to determine the expression and prognostic value of ISL-1 in gastric carcinoma. A nude mouse xenograft model was established to study the role of ISL-1 on cancer genesis and development in vivo. Overexpression of ISL-1 significantly enhanced the tumorigenicity of NIH3T3 cells in vivo. ISL-1 expression was evaluated using immunohistochemistry in 456 human gastric carcinoma and normal tissues. ISL-1 was significantly overexpressed in gastric adenocarcinoma compared with normal gastric tissues. ISL-1 expression was significantly associated with depth of invasion, lymph node metastasis, TNM stage, and histological grade (P < .05, χ(2) test). Positive ISL-1 expression was associated with poorer 5-year overall survival in gastric cancer (P = .001, log-rank test). Multivariate Cox regression analysis demonstrated that ISL-1 expression (P = .047) could be an independent prognostic factor for overall survival in gastric carcinoma. This study suggests that ISL-1 may be a useful prognostic biomarker and may represent a novel therapeutic target for gastric adenocarcinoma.