High expression of glucose-regulated protein 78 (GRP78) is associated with metastasis and poor prognosis in patients with esophageal squamous cell carcinoma

BACKGROUND Glucose-regulated protein 78 (GRP78) plays an important role in the invasion and metastasis of many human cancers. However, the role of this protein in the progression of invasion and metastasis in esophageal squamous cell carcinoma (ESCC) remains elusive. PATIENTS AND METHODS Immunohistochemistry and Western blot were performed to analyze GRP78 expression in 92 patients with primary ESCC. The correlation of GRP78 expression with clinicopathological factors was analyzed. In vitro, the expression levels of GRP78 were downregulated by small interfering RNA transfection in TE-1 and CaEs-17 ESCC lines. Cell invasion and migration assays were applied to determine the invasion and migratory abilities of ESCC cells. RESULTS Compared with GRP78 in adjacent normal esophageal tissues, GRP78 was overexpressed in ESCC tissues. High GRP78 expression was significantly correlated with positive lymph node metastasis (P=0.035) and advanced tumor stage (P=0.017). Survival analysis revealed that high GRP78 expression was significantly associated with shorter overall survival (P=0.037). In multivariate analysis, GRP78 overexpression was identified as an independent prognostic factor for overall survival (P=0.011). si-GRP78 can significantly decrease the GRP78 expression level and reverse the invasion and migratory abilities of ESCC cells in TE-1 and CaEs-17 cell lines. CONCLUSION These findings demonstrated that high expression of GRP78 was associated with disease progression and metastasis in ESCC and might serve as a novel prognostic marker for patients with ESCC.