Expression and significance of GRHL2 in esophageal cancer

Esophageal cancer (EC) is one of the most common causes of cancer-related mortality in the world. Although much effort has been made to improve the 5-year survival rate of patients with EC, it still remains low due to diagnosis at an advanced stage, aggressive local invasion, early metastasis, and resistance to chemotherapy. Although grainyhead-like 2 (GRHL2) has attracted interest since it has been recently identified as a novel suppressor of the epithelial-mesenchymal transition, clinical values of GRHL2 and its relationship with the metastasis-related factors, such as hypoxia-inducible factor 1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF), remain unclear. In order to investigate the expression of GRHL2, HIF-1 alpha, and VEGF, and their correlation with angiogenesis in EC, 63 patients with EC were examined. The expression of GRHL2, HIF-1 alpha, and VEGF in tumor tissues was higher than that in adjacent tissues and was associated with tumor differentiation. GRHL2 expression was significantly correlated with lymph node metastasis and invasion depth, whereas VEGF expression was associated with tumor (TNM) stage. A significant correlation was found between the expression of GRHL2 and HIF-1 alpha. The patients expressing low GRHL2 and high HIF-1 alpha showed significant reduction in both overall survival rate and disease-free survival rate. The results demonstrated that abnormal expression of GRHL2 is common in EC, and low expression of GRHL2 accompanied by a high expression of HIF-1 alpha indicates poor prognosis.