Expression Of Cdc7、MCM2as A Marker For Proliferation And Prognosis In Diffuse Large B Cell Lymphoma

Objective:Diffuse large B-cell lymphoma (DLBCL) is the major common subtype of lymphoma and accounts for30-40%of all lymphomas in adults of western country。In China, the incidence of DLBCL is increasing rapidly.It can be cured. However, Using comprehensive treatment only40-45%of these patients are cured. Although the International Prognostic Factor index(IPI) has permitted identification of subsets of patients with large variations in prognosis, many patients with the same IPI score have different clinical outcome. According to biological heterogeneities, DLBCL can be divided into different subgroups, such as germinal center B-cell-like (GCB) DLBCL and activated B-cell-like (ABC) DLBCL. It is necessary to find certain molecular markers to identify poor-risk patients more correctly. Thus, there is still significant opportunity for improving survival in DLBCL patients.Methods:From2008.1-2010.1, we collected the clinical data characteristics of60DLBCL patients in Tianjin Medical University Cancer Hospital. The clinical data including age, gender, ECOG performance status, Ann Arbor stage, IPI, bone marrow involvement, B symptom, Extranodal involvement, LDH level, therapy model, histology type, they were analyzed retrospectively. Clinical evaluation was done according to the standard. Followed-up to2010.3by telephones and letters. using IHC and real-time PCR to assess the Cdc7,MCM2gene expression.A statistical analysis is carried out of the association of Cdc7, MCM2and the clinico-pathological characteristics.OS rates were calculated according to the Kaplan-Meier method and differences between survival curves were evaluated using the log-rank test.The Cox proportional hazard regression model was used for univariate analyses. Multivariate analysis was performed using Cox regression model. The correlation of Cdc7and MCM2with IPI score, Ann-Arbor stage was used by Pearson correlation analysis. Statistical analyses were performed with SPSS16.0software.P<0.05was considered statistically significant.Result: 1、In univariate analysis,2-years overall survival of the patient with positive Cdc7expression is41%,and the patient with negative Cdc7expression is73%,(p=0.037);2-years overall survival of the patient with positive MCM2expression is25%,and the patient with negative MCM2expression is75%,(p=0.042); The patients with Cdc7and MCM2positive DLBCL had a higher stage of disease than patients with Cdc7and MCM2negative DLBCL. The patients with Cdc7and MCM2positive DLBCL had a higher IPI of disease than patients with Cdc7and MCM2negative DLBCL.2、The2-year survival rate of Cdc7with high/low level expression in peripheral blood is38.3%and65.4%(P=0.001),2-year survival rate of Cdc7with high/low level expression in bone marrow is37.2%and75.5%(P=0.032),2-year survival rate of MCM2with high/low level expression in peripheral blood is44.0%and68.2%(P=0.025),2-year survival rate of MCM2with high/low level expression in bone marrow is39.0%and63.4%(P=0.007)Conclusion:IPI、treatment and different cell derivation were prognosis factors, and poor disease specific survival is observed in DLBCL patients with high level expression of Cdc7,MCM2. Cdc7,MCM2expression can be used to assess tumor proliferation and may be useful as an additional marker when combined with traditional marker to refine the prediction of outcome in DLBCL.Besides,Cdc7%MCM2signal pathway maybe the therapeutic target of new drug for DLBCL lymphoma.