REV-ERBα reduction is associated with clinicopathological features and prognosis in human gastric cancer.

Gastric cancer is a serious threat to human health. Nuclear receptor subfamily 1 group D member 1 (REV-ERB) is a member of the nuclear hormone receptor family that regulates lipid metabolism, inflammatory responses and circadian rhythms. However, the role of REV-ERB in the pathogenesis of human gastric cancer is unclear. The present study employed gastric cancer tissues from 74 patients and determined the association between REV-ERB expression with clinicopathological variables and prognosis. Furthermore, the association between REV-ERB and apoptosis in undifferentiated and moderately differentiated human gastric cancer cells was determined. It was identified that REV-ERB expression was decreased in gastric cancer, which was positively associated with poor differentiation (P=0.009), T stage (P=0.001), Tumor-Node-Metastasis (TMN) stage (P=0.001) and lymph node metastasis (P=0.007). In the survival analysis, the 3- and 5-year survival times of patients were significantly associated with REV-ERB expression (P=0.009 and P=0.002, respectively). Low REV-ERB expression was associated with poor prognosis (P<0.05). Concurrently, cleaved caspase-3 expression was downregulated, whereas expression levels of Bcl-2 and the Bcl-2/Bax ratio were upregulated in gastric cancer tissues compared with normal tissues. REV-ERB activator GSK4112 caused apoptosis in SGC-7901 and BGC-823 cell lines. REV-ERB levels were decreased in human gastric cancer, which was associated with poor differentiation, TMN stages and poor prognosis. REV-ERB is a potential biomarker for tumor development and prognosis, and a potential therapeutic target for gastric cancer.