Expression And Significance Of ?-H2AX Protein In Diffuse Large B-cell Lymphoma

BackgroundDiffuse large B cell lymphoma(DLBCL)is the most common type of malignant lymphoma(ML),and its incidence accounts for about 90% of non-Hodgkin lymphoma(NHL))Of patients 30% to 40%,accounting for 45.8% of Chinese NHL patients.DLBCL showed great heterogeneity in histological morphology,clinical manifestations and prognosis.Although rituximab combined with chemotherapy improved the prognosis of patients with DLBCL to a certain extent,recurrence or progression was still found in 50% of DLBCL patients,unable to achieve complete remission.Studies have shown that some patients even received autologous hematopoietic stem cell transplantation(HSCT)treatment,the response rate was only20% to 40%,the effect is still not optimistic.Therefore,to explore deeper pathogenesis,more accurate prognosis stratification,to find new and more effective treatment targets and drugs have been becoming the current focus of attention.In recent years,most researchers agree that DNA damage repair is closely related to the occurrence and development of tumors.If the cells have DNA repair defects and / or repair system is inhibited,the tumor cells will be killed.At present,many DNA damage repair genes have been found,and ?-H2 AX can recruit a series of DNA damage repair proteins and signaling molecules.The ?-H2 AX is a phosphorylation roduct of histone H2 AX.It can be used in the identification of DNA damage,DNA repair process plays a key role.If DNA damage can not be repaired or repaired in time,it will lead to various deleterious mutations,genomic instability,leading to cell death,which may lead to tumor if occurring in higher eukaryotes.The phosphorylation level of H2 AX in tissues can reflect the stability of the genome.Currently,?-H2 AX analysis has been widely used in many oncology studies.However,the significance of ?-H2 AX expression in DLBCL has rarely been reported.In this study,we used immunohistochemistry to analyze the effect of ?-H2 AX protein expression on the prognosis of DLBCL and to explore the relationship between DNA damage and the possible pathogenesis of DLBCL.Object Applying immunohistochemical technique studies the expression of ?-H2 AX in diffuse large B-cell lymphoma and its relationship with disease prognosis,and explores the relevant mechanisms,providing a new reference for the diagnosis and treatment of DLBCL patients.Materials and Methods1.Collection of paraffin specimens: collected from May 2000 to October 2016 in Henan Province Tumor Hospital diffuse large B cell lymphoma pathological biopsy or surgical removal of paraffin specimens of 107 cases.2.Paraffin specimen treatment: Each paraffin specimen were cut into 2 pieces of about 2um thickness of the sheet,placed on a glass slide,one for HE staining,screening for HE-positive specimens corresponding immunohistochemical detection of ?-H2 AX expression.3.Interpretation of results: <10% of stained positive cells were negative(-),and>10% of stained positive cells were positive(+).4.Statistical Analysis: The test results were statistically analyzed by SPSS21.0statistical software.Qualitative data X2 test,Kaplan-Meier univariate survival analysis,and multivariate Cox regression tests were used to investigate the expression of ?-H2 AX and diffuse large B-cell lymphoma disease.The relationship of prognosis was P < 0.05 for the difference was statistically significant.Results1.1 Expression of ?-H2 AX Protein in Diffuse Large B Cell Lymphoma DiseaseOf the 107 patients with diffuse large B-cell lymphoma in this study,48 were positive for ?-H2 AX,with a positive rate of 44.9%.1.2 The relationship between the expression of ?-H2 AX protein and clinical characteristicsThere was no significant correlation between the expression of ?-H2 AX and gender,age,presence or absence of B symptoms,clinical stage,LDH level,and with or without extranodal involvement.It was significantly correlated with PS status and IPI score(P?0.05).1.3 Univariate survival analysis of clinical pathological features and disease prognosisAll the clinical pathological features involved in this study and the prognosis of LBCL were analyzed by Kaplan-Meier system.The results showed that the gender,age,and presence or not of B symptoms were not related to the prognosis of the disease.The P values were 0.104,0.309,and 0.250,respectively.The patient's PS status,IPI score,clinical stage,and ?-H2 AX protein were significantly associated with prognosis,with P values of 0.020,0.003,0.001,and 0.040,respectively;the data showed high ECOG scores,high IPI scores,and high clinical outcomes.Stages and positive expression of ?-H2 AX protein are all indicators of poor prognosis.1.4 Multi-factorial survival analysis of ?-H2 AX protein,PS status,IPI score,clinical stage and disease prognosisMultivariate survival analysis was performed by Cox regression analysis.The data showed that ?-H2 AX protein was an independent prognostic factor independent of clinical stage(P=0.027).Conclusions1.The protein expression of ?-H2 AX,clinical stage,IPI score,and PS status were related to the overall survival(OS)time of diffuse large B-cell lymphoma disease.2.The positive expression of ?-H2 AX and high clinical stage were independent risk factors influencing the prognosis of DLBCL.