The Expression And Clinical Significance Of G9a In Diffuse Large B-cell Lymphoma

Research BackgroundLymphoma is a malignant tumor that originates in lymph nodes or lymph tissues.Its pathology can show massive proliferation of tumorous lymphoid tissues with different differentiation and maturity,which can invade various parts or tissues of the body.Non-Hodgkin Lymphoma(NHL)accounts for the vast majority of lymphomas,among which Diffuse Large B cell Lymphoma(DLBCL)is the most common subtype of NHL,accounting for about 30%-40% of adult NHL.There are great differences in clinical characteristics,pathological tissue types,immunophenotypes,genetic characteristics and biological science behaviors.Different subtypes of DLBCL show obvious differences in response to treatment and prognosis.Although a series of new therapies such as molecular targeted drugs and cellular immunotherapy have improved the effectiveness of lymphoma treatment,some patients still face the problem of refractory relapse.It is particularly important to improve the prognosis stratification and formulate precise and individualized treatments.Therefore,it is necessary to further explore prognostic factors and find therapeutic targets.With the deepening of our research on lymphoma,the important role of epigenetic modification in its formation,occurrence and evolution has gradually been discovered.Among them,the epigenetic modification enzyme that has received much attention is histone methyltransferase(HMTs),HMTs is a class of S-adenosylmethioni Ile(SAM)as the methyl donor,which catalyzes the transfer of 1～3 methyl groups to histone lysine or arginine Methyltransferase.Among them,G9 a is the methyltransferase of lysine at position 9 of histone H3,which can methylate H3K9.The methylation of H3K9 will participate in DNA methylation,gene transcription inhibition and heterochromatin Formation and other processes,and these are very important in the occurrence and development of cancer.G9 a expression is abnormally increased in a variety of tumors,such as gastric cancer,bladder cancer,breast cancer,multiple myeloma,etc.,and is related to tumor proliferation,apoptosis,invasion and other biological functions.This study is intended to explore the expression of G9 a in DLBCL,analyze its clinical significance in DLBCL,and lay the foundation for finding new targets.PurposeTo compare the expression of G9 a in DLBCL and inflammatory hyperplastic lymphoid tissue,to explore and analyze the relationship between the expression level of G9 a and the clinical characteristics,pathological types and prognosis of patients with DLBCL.MethodCollected 75 cases of lymph node pathological specimens of newly treated DLBCL patients in the Affiliated Tumor Hospital of Zhengzhou University as the experimental group,and 25 specimens of inflammatory hyperplasia of lymph nodes were collected in the control group.Immunohistochemical method was used to detect the expression of G9 a protein in DLBCL tissue and lymph node inflammatory hyperplasia tissue specimens.The chi-square test was used to analyze the correlation between G9 a and the clinical characteristics of DLBCL patients,the Kaplan-Meier method was used for prognostic univariate analysis and the survival curve was drawn,and the prognostic multivariate analysis was analyzed by COX regression model.1.75 cases of DLBCL tissue,49 cases(65.3%)showed positive expression of G9 a protein,and 5 cases(20.0%)of 25 cases of inflammatory hyperplastic lymphoid tissue were positive for G9 a.The expression of G9 a in DLBCL was significantly up-regulated compared with lymph node reactive hyperplasia tissue.And the difference was statistically significant(P<0.001).2.There was no significant difference in gender,age,B symptoms,and LDH levels between G9 a positive and G9 a negative patients(P>0.05).The value of β2macroglobulin、Ann Arbor staging and Ki-67 in patients with positive G9 a protein expression,was higher than those of patients with negative G9 a protein expression,and the differences were statistically significant(P=0.041,0.019,0.044)3.After initial treatment,of the 49 G9 a protein-positive patients,29(59.2%)achieved CR,20(40.8%)did not achieve CR,and 18 of 26 G9 a protein-negative patients achieved CR(69.2%),8 cases(30.8%)did not reach CR,the difference was not statistically significant(P=0.233).It shows that is no significant difference between the G9 a protein positive group and the negative group in terms of complete remission after initial treatment.4.Of the 75 patients,46 were in the GCB group,26 were G9 a positive and 20 were G9 a negative;29 were in the Non-GCB group,23 were G9 a positive,and 6 were G9 a negative;the G9 a expression rate of Non-GCB was higher than that of the GCB group(79.3%vs56.5%),and the difference was significant(P=0.023<0.05).5.Follow-up of 75 DLBCL patients,a total of 74 complete data were obtained.Survival analysis of these cases showed that the 3-year OS of the G9 a protein negative group and the G9 a protein positive group were 89.5% and 74.4%,respectively,and there was a difference between the two groups.It is statistically significant(P=0.043<0.05).The 3-year PFS of the G9 a protein negative group and the G9 a protein expression positive group were 79.3% and 59.4%,respectively,and the difference between the two groups was statistically significant(P=0.038<0.05).It indicates that the positive expression of G9 a protein is a poor prognostic factor affecting OS and PFS in newly treated DLBCL patientsConclusion1.Compared with inflammatory hyperplastic lymphoid tissue,the expression of G9 a protein in DLBCL is significantly increased.2.The β2 microglobulin value,Ann Arbor staging,and Ki-67 index of DLBCL patients with positive G9 a protein expression are higher than those of patients with negative G9 a protein expression,indicating that the over expression of G9 a may be related to the proliferation and invasion of DLBCL tumor cells.3.Positive G9 a protein expression is a poor prognostic factor that affects 3-year OS and PFS in newly treated DLBCL patients,but it is not an independent prognostic factor.