组蛋白去乙酰化酶3表达与胃癌的临床相关性研究

Study of the clinical relevance between HDAC3 expression and gastric cancer

目的研究组蛋白去乙酰化酶3(HDAC3)表达与胃癌发生、发展和预后的相关性。方法选择一款含111例胃癌病例样本且携带随访信息的胃癌组织芯片,采用免疫组织化学方法检测HDAC3蛋白的表达,采用SPSS20.0统计学软件分析实验数据和胃癌样本临床指标及预后的相关性。结果 HDAC3特异性地表达在胃癌样本的细胞核,其在胃癌组织中的表达阳性率显著高于癌旁组织(P=0.001)。临床指标相关性分析发现:HDAC3表达和胃癌病人的T分期、N分期、M分期、临床分期等临床指标均分别呈正相关,差异有统计学意义(均r>0.2,均P<0.05)。随后的生存分析也证实:HDAC3高表达的胃癌患者的预后显著更差(6.3%vs.22.0%,P=0.029);另外,年龄、肿瘤大小、病理分级、T分期、N分期和临床分期等指标也分别和胃癌患者的预后呈显著负相关,差异有统计学意义(均P<0.05)。将上述7个预后相关指标纳入COX多因素回归分析,结果显示:只有T分期是胃癌的独立预后因子(P=0.043),HDAC3等其他指标都不是胃癌的独立预后因子(均P>0.05)。结论HDAC3高表达的胃癌细胞可能具有更强的侵袭和迁移能力,更容易向周围和远处组织器官侵润和转移,并因此降低了胃癌患者的生存期;也可能上述促癌过程受到其他基因和信号网络的调控,而HDAC3在其中未能起到主导作用。

Objective To study the correlation between the expression of HDAC3 and the occurrence, development and prognosis of gastric cancer. Methods The gastric cancer tissue microarray containing 111 samples with following-up information was utilized. The expression of HDAC3 protein was detected by immunohistochemistry and the correlation between the experimental data and clinical parameters as well as prognosis of gastric cancer was analyzed by SPSS software. Results HDAC3,specifically expressed in the nucleus,was significantly higher in gastric cancer tissues than para-carcinoma tissues（P = 0. 001 ）. Clinical index correlation analysis showed that HDAC3 expression was positively correlated with T staging, M staging, N staging and clinical staging of gastric cancer patients significantly （ r 〉 0.2, P 〈 0.05 ）. Subsequent survival analysis also confirmed that the prognosis of patients with high HDAC3 expression were significantly worse （ 6.3 % vs. 22.0% , P = 0.029 ）, in addition, age, tumor size, histological grade, T stage, N staging and clinical staging index were also significantly negative correlated with patients＇ survival time （ P 〈 0.05 ）. Then, we included these seven prognostic factors in the Cox multivariate regression analysis. The results showed that only the T staging（ P = 0.043 ） but not HDAC3 and all other indicators was independent prognostic factor （ P 〉 0.05 ）. Conclusion We speculate that the gastric cancer cells over-expressing of HDAC3 may have stronger invasion and migration ability, and could be easily transferred to the surrounding and distant tissues and organs, thus reducing the patient＇ s lifetime. It is also possible that HDAC3 might be not in the leading role in this cancer promoting process which may be regulated by other gene and signaling network. Next, we plan to establish HDAC3 over expression gastric cancer cell lines, giving anticaneer drugs and HDAC3 inhibitor treatment, in order to further study the specific molecular signaling network of HDAC3 in gastric cancer.