High expression of cAMP-responsive element-binding protein 1 (CREB1) is associated with metastasis, tumor stage and poor outcome in gastric cancer

Abstract

cAMP responsive element binding protein 1 (CREB1) has been reported to be implicated in tumor development and progression of human cancers. However, the clinical significance and regulatory mechanisms of CREB1 expression in gastric cancer remain largely unknown. In the present study, immunohistochemistry was performed to detect the expression of CREB1 protein in 185 primary gastric cancer tissues, 50 secondary lymph node metastatic foci and 50 nontumorous gastric tissues. A prognostic model combining CREB1 expression with TNM tumor stage was constructed by logistic regression analysis. Regulation of CREB1 by miRNAs was investigated by luciferase reporter assay and Western blot. It was shown that CREB1 was highly expressed and correlated with lymph node metastasis, distant metastasis and tumor stage and poor outcome in gastric cancer. The prognostic model was proven to be an independent prognosis predictor and performed better than CREB1 or tumor stage alone. CREB1 was identified as a direct target of miR-27b and miR-200b, and down-regulated by miR-27b/miR-200b. We conclude that CREB1 is a promising biomarker to predict tumor metastasis and patient outcome in gastric cancer, and the miR-27b/miR-200b-CREB1 pathway may serve as a potential molecular target for the treatment of gastric cancer.