H3K27的三甲基化蛋白在初治弥漫大B细胞淋巴瘤的表达及对预后的影响

Expression and Prognostic Significance of H3K27 Trimethylation Protein in DLBCL

目的:探讨H3K27me3在弥漫大B细胞淋巴瘤(DLBCL)中的表达及对预后的影响。方法:收集福建省肿瘤医院102例初治DLBCL石蜡标本,利用TMA技术制成组织芯片,免疫组织化学方法检测H3K27me3等蛋白的表达,收集临床数据和随访信息,用Kaplan-Meier法分析治疗水平,用Cox比例风险模型分析预后因素,比较不同表达与患者临床病例特征及预后关系。结果:DLBCL组织芯片位点完整。H3K27me3高表达者占59.8%,与老年(>60岁)、ECOG≥2、侵犯结外病灶数目≥2、高LDH、IPI高-中风险组相关。H3K27me3高表达组治疗完全缓解(CR)率和总有效(OR)率均低于低表达组,分别为20%vs 57.5%和41.8%vs 90%(P<0.001);高表达组中位生存时间21.5个月,较低表达组中位生存期明显缩短(P<0.0001)。COX多因素分析显示,H3K27me3高表达是DLBCL预后不良的危险因素(P=0.007)。结论:TM A技术可用于DLBCL组织芯片构建,部分DLBCL存在H3K27me3高表达。该类型患者对治疗反应差,生存期短,检测H3K27me3蛋白表达对预测DLBCL预后具有一定临床价值。

Objective：To investigate the expression and prognostic effect of H3K27 trimethylation protein（H3K27me3） in diffuse large B-cell lymphoma（DLBCL）.Methods：A total of 102 DLBCL patients from Fujian Provincial Cancer Hospital were enrolled in this study.No therapy had been given before specimen collection.Tissue microarray（TMA） technique and immunohistochemistry（IHC） method were used for H3K27me3 immunostaining.Clinicopathologic and suvival data were carefully collected.The association between tested markers,clinicopathologic characteristics and prognosis were evaluated.Survival rates were analyzed by the Kaplan-Meier method,and prognostic factor were analyzed by the Cox proportional hazards model,the relation of different expression levels with clinical feature and prognosis of patients was compared.Results：The quality of TMA was perfect and meet the standard of analysis.Among all DLBCL patients,59.8%were characterized with high expression of H3K27me3,correlated with age,ECOG≥2,extranodular disease number ≥2,elevation of LDH,medium-high risk IPI.Patients with high H3K27me3 expression manifested that the complete remission rate（CR） and overall remission rate（OR） were lower than those of patients with low expression,i.e.,20%vs.57.5%and 41.8%vs.90%,respectively（P〈0.001）.In addition,patients with high H3K27me3 expression showed shorter median survival time,i.e.,21.5 mon（P〈0.0001）.Multivariate analysis indicated that H3K27me3 was an independent risk factor for DLBCL patients（P=0.007）.Conclusion：TMA technique is valid for the construction of DLBCL tissue chips.Patients with high expression of H3K27me3 indicates little response to treatment,worse outcome and shorter overall survival.The detection of H3K27me3 expression possesses a certain clinical value for prediction of DLBCL outcome.