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

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 low expression groups (P<0.001), moreover OS and PFS rates also were lower than those in low expression (P<0.001). In the RCHOP subgroup, the patients with EZH2 low expression 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 low expression or without coexpression. The patients with EZH2 low expression usually responde well to RCHOP regimen in the short-term or long-term survival.

[Expression and Prognostic Significance of H3K27 Trimethylation Protein in DLBCL].

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.