Department of Gastroenterology, the First People's Hospital of Yancheng, Yancheng 224005, China.
Department of Gastroenterology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221006, China.
Hum Pathol. 2019 Mar;85:194-201. doi: 10.1016/j.humpath.2018.10.031. Epub 2018 Nov 27.
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 (HDAC1) staining was seen in 60.7% patients with GCs, which was significantly greater than was seen in normal epithelial cells (19.4%; P < .005). HDAC1 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, HDAC1 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. HDAC1 expression was also an independent adverse prognostic factor for overall survival and disease-free survival.
组蛋白去乙酰化酶 1（HDAC1）与肿瘤的发生发展密切相关。本研究旨在探讨其对胃癌（GC）患者生存及生物学行为的影响。本研究分析了 252 例原发性 GC 肿瘤组织样本和体外研究中的 HDAC1 表达和糖酵解活性。结果显示，60.7%的 GC 患者存在高 HDAC1 染色，明显高于正常上皮细胞（19.4%；P <.005）。HDAC1 表达与肿瘤体积较大（P =.001）、T 分期较晚（P =.001）、淋巴结转移（N 分期；P <.001）和血管淋巴管侵犯（P =.005）相关。单因素和多因素生存分析显示，HDAC1 表达是疾病无进展生存和总生存的独立预后因素（P <.05）。体外研究显示，HDAC1 敲低细胞的糖酵解率明显降低。在患者样本中，HDAC1 表达总是伴随着高最大标准化摄取值（SUVmax）值（P <.05）。缺氧诱导因子（HIF）-1α反应元件-荧光素酶报告系统显示，HDAC1 以剂量依赖的方式影响 HIF1α 活性。综上所述，HDAC1 促进 GC 中的糖酵解，并影响肿瘤进展和转移过程中的 HIF-1α 活性。HDAC1 表达也是总生存和无病生存的独立不良预后因素。
