H3K4me3高表达与肝癌患者较差生存预后相关  

The clinical significance of H3K4me3 overexpression in prognosis of HCC patients

作　　者：伍刚[1] 何传超[2] Wu Gang;He Chuanchao

机构地区：[1]电子科技大学附属医院,四川省人民医院肝胆外科,四川成都610072 [2]中山大学孙逸仙纪念医院肝胆外科,广东广州510120

出　　处：《现代肿瘤医学》2018年第6期893-899,共7页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:81302161)

摘　　要：目的:探讨检测肝癌组织中组蛋白第三亚基四号赖氨酸的三甲基化(H3K4me3)蛋白的表达与肿瘤病理特点和肝癌患者生存预后的相关性。方法:免疫组化和Western-blot检测H3K4me3和组蛋白甲基转移酶(SET and MYND domain-containing protein 3,SMYD3)在肝癌组织(n=168)和细胞株中的表达。此外,实验结果还在另外一个肝癌组织芯片(n=147)中进行验证。H3K4me3表达的最佳分界点(optimal cut-point)由X-tile程序确定,患者的预后由Kaplan-meier生存曲线描述。结果:H3K4me3高表达于肝癌细胞系和肝癌组织,其高表达与肝癌尤其是早期TNM1/2期患者的较差总体生存显著相关。单因素和多因素分析均提示H3K4me3表达水平是患者预后的独立危险因素。此外,H3K4me3和SMYD3在两组肝癌组织中均存在正相关表达。结论:H3K4me3表达水平能成为肝癌患者术后生存的预测因子,其高表达可能与SMYD3有关。Objective:Purposes aberrant epigenetics including DNA methylation and histone modifications are involved in hepatocarcinogenesis,drugs targeting epigenetics dysfunction achieved promising progression in clinical trials.H3K4me3 always activates gene expression transcriptionally.Methods:The expression of H3K4me3 and SMYD3 was examined in HCC(hepatocellular carcinoma)cell lines and tissues(n=168),while the results were validated by another set of HCC tissues(n=147).The optimal cut-point of H3K4me3 expression was determined by X-tile program,while the HCC patients overall survival was evaluated by Kaplan-meier analysis.Results:H3K4me3 overexpressed in HCC cell lines and tissues,which was correlated with the poor total survival especially TNM I/II HCC patients.Besides,both univariate and multivariate analysis suggested that enhanced H3K4me3 expression was an independent predictor of reduced patients overall survival.Additionally,H3K4me3 expression was positively correlated with SMYD3 in both 2 sets of HCC tissues.Conclusion:H3K4me3 is a valuable predictor of post-operative survival of HCC patients,overexpression of which might be catalyzed by SMYD3.

关 键 词：肝细胞癌 H3K4me3 SMYD3 生存 预后 

分 类 号：R735.7[医药卫生—肿瘤]