H3K27me3和EZH2在弥漫大B细胞淋巴瘤疗效预测中的意义

Significance of H3K27me3 and EZH2 in Predicting the Therapeutic Efficacy of Diffuse Large B-Cell Lymphoma

目的:探讨H3K27me3及其甲基转移酶EZH2在对弥漫大B细胞淋巴瘤(DLBCL)近期疗效和远期预后的预测意义。方法:收集福建省肿瘤医院102例初治DLBCL石蜡标本,利用TMA技术已制成的组织芯片,应用免疫组织化学方法检测H3K27me3、EZH2、BCL-2等蛋白表达,收集临床治疗后评价情况和随访信息,并结合组织芯片检测H3K27me3、EZH2、BCL-2表达情况,生存分析应用Kaplan-Meier法,Pearson相关性分析EZH2与H3K27me3表达及BCL-2的相关性,spearman相关分析上述指标与不同疗效间的相关性,比较EZH2、H3K27me3表达及两者共表达与患者疗效及预后关系。结果:EZH2高表达者占61.8%,与H3K27me3及BCL-2蛋白高表达均正相关。H3K27me3高表达及H3K27me3/EZH2共表达组完全缓解(CR)和总有效(OR)率均低于低表达组(P<0.001),OS、PFS均差于低表达组(P<0.001);在RCHOP组中,EZH2低表达者CR和OR率均高于高表达者(P=0.003,P=0.019),OS和PFS均优于高表达者。结论:在部分DLBCL存在EZH2高表达及H3K27me3/EZH2共表达,该类型治疗反应差,生存期短。EZH2低表达患者群体使用RCHOP方案的近期疗效及远期生存率较高表达者有改善。

Objective： To investigate the significance of H3K27me3 and its methyltransferase EZH2 in predicting the short-term and long-term outcome of newly diagnosed patients with diffuse large B-cell lymphoma（ DLBCL）.Methods： The paraffin wax speciments of 102 DLBCL patients in Fujian Medical University Cancer Hospital were collected. The expression of H3K27me3,EZH2 and BCL-2 protein were detected using tissue array made by tissue microarray（ TMA） technique and immunohistochemistry method. The evaluation data after clinical treatment and follow-up results were collected and combined with expression levels of H3K27me3,EZH2 and BCL-2 detected by tissue array,then on the basis of these data,the survival of patients was analyzed by Kaplan-Meier method,the correlation of EZH2 with H3K27me3 and BCL-2 was analyzed by pearson correlation test,the correlation of above mentioned indicators with different therapeutic efficacy was analyzed by spearman correlation test. The relationship of H3K27me3 and EZH2 expression as well as co-expression of H3K27me3 and EZH2 with the therapeutic efficacy and prognosis of patients were compared. Results： A total of 61. 8% patients showed EZH2 high expression which positively correlated with high expression of H3K27me3 and BCL-2. The complete remission（ CR） and overall remission（ OR） rates in H3K27me3 high expression and co-expression of H3K27me3 EZH2 groups were lower than those in lowexpression groups（ P〈0. 001）,moreover OS and PFS rates also were lower than those in lowexpression（ P〈0. 001）. In the RCHOP subgroup,the patients with EZH2 lowexpression showed significantly better CR,OR OS and PFS in comparison with those of patients with higher expression（ P = 0. 003,P = 0. 019）. Conclusion： Part of DLBCL patients with H3K27me3 high expression or coexpression of both H3K27me3 and EZH2 exhibit a worse prognosis in comparison with those patients with H3K27me3 lowexpression or without coexpression. The patients with EZH2 lowexpression usually responde well to RCHOP regimen in the short-term or long-term survival.