He Qing, Li Guoqiang, Wang Xin, Wang Shubin, Hu Jiang, Yang Lang, He Yuqi, Pan Yuanming, Yu Dedong, Wu Yun
Inner Mongolia Medical University, Hohhot, China.
Department of Oncology and Translational Medicine Center, Baotou City Central Hospital, Baotou, China.
Cell Physiol Biochem. 2017;42(4):1326-1335. doi: 10.1159/000478961. Epub 2017 Jul 13.
Histone deacetylase 6 (HDAC6) plays a role in the progression of many tumors. However, the relationship between the level of HDAC6 expression and gastric tumorigenesis is still unclear. Here, we illustrate the potential correlation between Helicobacter pylori (HP) infection and the variation of HDAC6 expression in different gastric lesions, as well as the clinical significance of HDAC6 expression in gastric cancer (GC) patients.
Between 2011 and 2016, 364 patients with different types of gastric lesions were enrolled in Baotou City Central Hospital. Immunostaining of HDAC6 expression and HP infection were performed in the following cohort including 21 normal tissues (Normal); 40 samples with chronic superficial gastritis (CSG); 106 with chronic atrophic gastritis (CAG); 94 with intestinal metaplasia (IM); 64 with dysplasia (DYS) and 39 with gastric cancer (GC). Survival analysis was performed in another 80 GC patients using the Kaplan-Meier method and multivariate Cox regression analyses. The level of HDAC6 expression was determined by Real-time PCR, Western blotting and IHC staining in gastric cell lines and tissues. Furthermore, the correlation between HDAC6 expression and clinicopathological features and prognosis was analyzed in the GC cohort. HP strains were lavaged into Kunming mice to investigate the effects of HP infection on the expression of different HDAC members in this mouse model.
Higher levels of HDAC6 expression were detected in normal and premalignant lesions than in the GC tissues (p<0.01), and decreased HDAC6 expression was associated with HP infection and TNM stage (p<0.01 and p=0.048, respectively). Multivariate analysis revealed that HDAC6 expression was an independent predictor of the outcome of GC patients (p=0.04). HP mediated HDAC6 expression in the cell lines and KM mice. HP infection could promote HDAC1 and HDAC4 expression as determined by Western blotting.
HDAC6 is a promising biomarker for early diagnosis and prognosis during the oncogenic transformation of gastric cancer.
组蛋白去乙酰化酶6（HDAC6）在多种肿瘤进展中发挥作用。然而，HDAC6表达水平与胃癌发生之间的关系仍不清楚。在此，我们阐述幽门螺杆菌（HP）感染与不同胃病变中HDAC6表达变化之间的潜在相关性，以及HDAC6表达在胃癌（GC）患者中的临床意义。
2011年至2016年期间，包头市中心医院纳入了364例不同类型胃病变患者。对以下队列进行HDAC6表达和HP感染的免疫染色，包括21例正常组织（正常）；40例慢性浅表性胃炎（CSG）样本；106例慢性萎缩性胃炎（CAG）；94例肠化生（IM）；64例发育异常（DYS）和39例胃癌（GC）。使用Kaplan-Meier方法和多变量Cox回归分析对另外80例GC患者进行生存分析。通过实时PCR、蛋白质印迹法和免疫组化染色测定胃细胞系和组织中HDAC6的表达水平。此外，在GC队列中分析HDAC6表达与临床病理特征及预后之间的相关性。将HP菌株灌胃到昆明小鼠体内，以研究HP感染对该小鼠模型中不同HDAC成员表达的影响。
在正常和癌前病变中检测到的HDAC6表达水平高于GC组织（p<0.01），HDAC6表达降低与HP感染和TNM分期相关（分别为p<0.01和p=0.048）。多变量分析显示，HDAC6表达是GC患者预后的独立预测因子（p=0.04）。HP介导细胞系和KM小鼠中的HDAC6表达。蛋白质印迹法测定结果表明，HP感染可促进HDAC1和HDAC4表达。
HDAC6是胃癌致癌转化过程中早期诊断和预后的有前景的生物标志物。
