Histone deacetylase-1 as a prognostic factor and mediator of gastric cancer progression by enhancing glycolysis

Abstract

Histone deacetylase 1 (HDAC1) has been shown to be closely associated with tumor development. We investigated its effects on survival and biological behavior in gastric cancer (GC). HDAC1 expression and glycolysis activity were analyzed in a cohort of 252 samples of primary GC tumors and in vitro study. High HDAC1 (HDAC1High) staining was seen in 60.7% patients with GCs, which was significantly greater than was seen in normal epithelial cells (19.4%; P < .005). HDAC1High expression was associated with larger tumor size (P = .001), advanced T stage (P = .001), lymph node metastases (N stage; P < .001), and lymphovascular invasion (P = .005). Univariate and multivariate survival analyses showed HDAC1 expression to be an independent prognostic factor for both disease-free survival and overall survival (P < .05). In vitro studies showed a notably decreased glycolysis rate in HDAC1 knockdown cells. In patients' samples, HDAC1High expression was always accompanied with high Maximal standardized uptake value (SUVmax) value (P < .05). A hypoxia-inducible factor (HIF)-1α response element-luciferase reporter system showed HDAC1 to affect HIF1α activity in a dose-dependent manner. In conclusion, HDAC1 promotes glycolysis in GC and affects HIF-1α activity in tumor progression and metastasis. HDAC1High expression was also an independent adverse prognostic factor for overall survival and disease-free survival.