Prognostic Value of Sonic Hedgehog Protein Expression in Gastric Cancer

Abstract

Sonic hedgehog is produced in gastric epithelial cells and plays a crucial role in parietal cell function and the regulation of gastric epithelial cell differentiation. Emerging evidence suggests that the sonic hedgehog pathway is not only involved in the development of cancers but also in their progression and aggressiveness. To assess its prognostic value in gastric cancer, sonic hedgehog protein expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising 319 human gastric cancer specimens. Cytoplasmic sonic hedgehog expression was scored from 0 to 4, reflecting the percentage of sonic hedgehog-positive cells. Specimens were classified into two groups according to their sonic hedgehog score: those with a score ranging from 0 to 3 were considered low expressers and those with a score of 4 were considered overexpressers. The sonic hedgehog overexpression group included more patients with early gastric cancer than the low sonic hedgehog expression group (25.9 vs. 74.1, P 0.000). Sonic hedgehog expression was lower in patients with lymph node metastasis than in patients without lymph node metastasis (31.4 vs. 68.4, P 0.02). Similarly, patients with a lower TNM stage showed significantly higher sonic hedgehog expression. In addition, the survival time of patients with sonic hedgehog overexpression was significantly prolonged (69.27 1.39 months) compared with that of patients with low sonic hedgehog expression (61.23 2.04 months, log-rank test, P 0.03). These results indicate that sonic hedgehog overexpression may be a marker of good prognosis in gastric cancer.