Expression Of The Autophagy Related Proteins Beclin-1 And P62 In Diffuse Large B Cell Lymphoma And Its Prognostic Significance

Objective:The study was designed to detect the levels of the auto phagy related proteins Beclin-1 and P62 expression in patients with diff use large B cell lymphoma(DLBCL),The correlation between the level of Beclin-1 and P62 expression and the clinical characteristics of DLB CL patients was analyzed,and explore the relationship between Beclin-1 and P62 and the pathogenesis of DLBCL,so as to provide the theoreti cal basis for differential diagnosis,prognosis judgment and selection of new therapeutic targets.Methods:From January 2014 to January 2019,28 cases of DLBCL patients with complete clinical data and pathological specimens of lymph nodes were selected as the experimental group.At the same time,the lymph node pathological specimens from 10 cases of RLD patients were select ed as the control group.The expression levels of Beclin-1 and P62 in t he experimental group and the control group were detected by immunoh istochemistry.The levels of Beclin-1 and P62 expression between the ex perimental group and the control group were compared.At the same ti me,the correlation between the different clinical characteristics of DLB CL patients and the levels of Beclin-1 and P62 expression was analyzed, and the prognosis influence of Beclin-1 and P62 for DLBCLpatients w as further analyzed.Result:1.The results of immunohistochemistry showed that Beclin-1 and P62 were highly expressed in DLBCL and RLD patients,and the protein was mainly located in the cytoplasm of lymphocytes,which was yellow or brown deep stained granules.2.The expression level of Beclin-1 in RLD was higher than that in DLBCL,but there was no significant difference between them(P>0.05).The expression level of P62 in DLBCL was significantly higher than that in RLD.On the contrary,the difference between them is statistically significant(P<0.05).3.There was no correlation between the expression of Beclin-1 and P62 protein and the age,gender,Bcl-2 and pathological subtype of DLBCL patients(P>0.05).The expression level of Beclin-1 was only related to the Ann Arbor stage(P < 0.05).While the expression level of P62 was significantly different from that of Ann Arbor stage,IPI score,presence or absence of extranodal lesions,Ki-67 index and LDH level in DLBCL(P<0.05),which is suggested that the expression level of P62 may be used as a good biological index to judge the prognosis of DLBCL.4.In the experimental group,28 DLBCL patients were treated with 6-8 standard R-CHOP chemotherapy,followed up in outpatient or inpatient for short-term efficacy evaluation(overall response rate: CR + PR rate)and long-term efficacy evaluation(replase + disease progression rate).The results showed that the expression level of Beclin-1 and P62 did not affect the short-term efficacy of the patients.There was no significant difference between the two groups in ORR(P> 0.05);In terms of long-term efficacy,the relapse and progression rate of patients in Beclin-1 high expression group was significantly lower than that of low expression group(P<0.05).In contrast,the relapse and progression rate of patients in P62 high expression group was significantly higher than that of low expression group(P<0.05).It is suggested that inhibition of autophagy may increase the risk of drug resistance and immune escape of tumor cells,and affect the therapeutic effect of DLBCL patients.Our data showed that the decreased autophagy level of tumor cells is an independent risk factor for poor prognosis of DLBCL.Conclusions:1.Compared with RLD,the expression levels of Beclin-1 and P62 in DLBCL has no significant difference,while the expression level of P62 is significantly higher than RLD,which indicates that P62 protein can be used as one of the indicators to distinguish DLBCL and RLD.2.Subgroup analysis showed that the expression levels of Beclin-1 and P62 had no correlation with age,gender,bcl-2 level and pathological subtype of DLBCL patients.The expression level of Beclin-1 was only correlated with the Ann Arbor stage of DLBCL,while the expression of P62 was correlated with the Ann Arbor stage,IPI score,presence or absence of extranodal lesions,Ki-67 index and LDH level in DLBCL patients,which confirmed that the expression level of P62 protein played an important role in judging the prognosis of DLBCL.3.In terms of efficacy judgment,the expression of Beclin-1 and P62 has no significant effect on the short-term efficacy of DLBCL patients.The patients with low expression of Beclin-1 have a high relapse and progression rate,with a short survival period.In contrast,patients with high expression of P62 have a higher relapse and progression rate,and a shorter survival period.It is suggested that autophagy state of lymphoma cells in DLBCL patients affects the long-term prognosis.The decresed autophagy level in DLBCL patients lower the long-term survival rate.4.According to the results of this study,patients with high expression of P62 protein have higher risk of DLBCL prognosis stratification,and the long-term efficacy of patients with high expression of P62 protein is worse.Targeted knockout of P62 gene in patients with P62 high expression may be a new target for the treatment of refractory and relapse patients in the future.