The Correlation Study Of MYC,BCL2 And P53 Expressions And Prediction Of Chemotherapy Response In Diffuse Large B Cell Lymphomas

BackgroundThe incidence of lymphoma grows continuously.At present,lymphoma is one of the common malignant tumors,and diffuse large B cell lymphoma(DLBCL)is the most common subtype of lymphoma.At present,chemotherapy is still the main method for the treatment of DLBCL,and about 60% of the patients with DLBCL can be cured by immunochemotherapy.About 40% of DLBCL patients failed in chemotherapy.There are many factors leading to the failure of chemotherapy.It is believed that the drug resistance of tumor cells to chemotherapeutic drugs is the main reason for the failure of chemotherapy,and may be related to the overexpression of some proteins on the tumor cell membrane or the surface of the nucleus.In recent years,the study found that MYC and BCl2 protein expression of the poor prognosis of patients with DLBCL patients.While in chronic lymphocytic leukemia patients treated with chemotherapy and associated with P53 gene mutation has a poor prognosis.Whether MYC protein,BCL2 protein and the expression of P53 in DLBCL are related to resistance to chemotherapy,are still unclear,and will be investigated here in this study.ObjectiveThe analysis of the initial chemotherapy effect and MYC,BCL2 and P53 protein expressions in the sample tissues of diffuse large B cell lymphoma.The possible mechanism of chemotherapeutic drug resistance is discussed objectively and efficiently.Patients and methodsThe clinical data of 137 patients with DLBCL diagnosed in the second hospital of Dalian Medical University from June 2014 to June 2017 were collected.According to the classification of WHO in 2008,all patients were diagnosed with DLBCL by histopathology.Patients with primary central nervous system lymphoma,loss of follow up after surgery,less than four cycles of chemotherapy,and patients who failed to meet the immunohistochemical requirements of the study were excluded.Only 48 cases of qualified cases were left.The patients(48)were divided into two groups according to the efficacy of chemotherapy.The first group was complete remission(CR)and unconfirmed complete remission(CRu)group and considered as CR+Cru group,the other group was partial remission(PR),stable(SD)and ineffective(PD)and considered as non-CR group.All specimens were specimens before chemotherapy.The immunohistochemical method was used to analyze the protein expression of MYC,BCL2,and P53 in tumor specimens.All the results of the immunohistochemical analysis were without any clinical intervention.According to the related literature,the cutoff values of MYC,BCL2 and P53 protein positive were set at 40%,50%,and 30% of the stained tumor cells respectively.The relationship between the expression of MYC,BCL2 and P53 protein and the short-term efficacy of chemotherapy was analyzed.The data analysis uses the statistical software SPSS 22 to compute all descriptive statistics.Chi-square and Mann Whitney U test were used to evaluate the correlation between the clinical features and the expression of MYC,BCL2,and P53 protein.P <0.05 is considered to be statistically significant.ResultsThis study retrospectively analyzed age,sex,LDH,stage,IPI score,cell source(germinal centre B cell GCB and non germinal centre B cell non GCB),beta-2 microglobulin and ESR level on the efficacy of chemotherapy,only ESR,and staging were associated with complete remission in chemotherapy CR+CRu group(P = 0.02,P = 0.05).13 cases(27%)were overexpressed by MYC.BCL2 overexpression in 18 cases(38%),P53 overexpression in 17 cases(35%).After first-line chemotherapy,only the overexpression of MYC protein was associated with the clinical CR+CRu response(P = 0.05),and the overexpression of MYC protein was low in CR+CRu.There was the statistically insignificant difference in the correlation between the overexpression of BCL2 or P53 and the clinical response(P =0.96,P = 0.75).There was a significant difference in the group of CR+CRu between MYC+ / P53+ and MYC-/ P53-DLBCL patients(p=0.03).The combined overexpression of MYC + / BCL2 + was compared with MYC-/ BCL2-,and there was no significant difference in the clinical CR+CRu group after the first-line chemotherapy(p=0.22).There was no statistical difference in the therapeutic effect of BCL2 + / P53 + and BCL2-/ P53-in the chemotherapy of DLBC patients(P = 1.00).Mann-Whitney U test was used to detect the effect of MYC,BCL2 and P53 expression rate on the CR+Cru rate of DLBCL patients at the 40%,50%,and 30% truncated values,respectively,and the results were p=0.93,p=0.99 and p=0.37 respectively.It is suggested that the low expression of MYC,BCL2 and P53 protein does not affect the short-term efficacy of chemotherapy in DLBCL patients.Conclusion1.The retrospective analysis suggested that the short-term effect of chemotherapy in patients with advanced stage and ESR high DLBCL was poor.2.The short-term efficacy of MYC protein overexpression in DLBCL patients was weak,suggesting that the overexpression of MYC protein may play important role in chemotherapeutic resistance.3.MYC and P53 protein overexpressed DLBCL patients had the worst short-term effect of chemotherapy,suggesting that MYC protein and P53 protein may play a synergistic role in induction chemotherapy resistance.