Expression And Significance Of Activation-induced Cytidine Deaminase In HBV-associated Diffuse Large B-cell Lymphoma

Objective Diffuse large B-cell lymphoma(DLBCL)is one of the most common non-Hodgkin's lymphomas,accounting for 30%-40%.Studies on the etiology of lymphoma indicate that viral infection is a major risk factor.A large number of studies have shown that hepatitis B virus(HBV)infection is associated with DLBCL,but the clearly pathogenesis is unknown.Activation-induced cytidine deaminase(AID)induces cytosine deamination to form uracil.Through the process of somatic mutation and class switching of immunoglobulin(Ig)genes,antibody affinity maturation and diversity are produced,and the adaptive immune response is involved.In recent years,genome-wide sequencing analysis found that AID can target non-Ig gene and induce mutations or chromosomal translocations which play a key role in the development of lymphomas.Therefore,this article will explore the expression and clinical significance of AID in HBV-related DLBCL tissues,and lay the foundation for the exploration and treatment of subsequent related pathogenesis.Methods The clinical data of 94 newly diagnosed DLBCL patients were retrospectively analyzed and the expressions of AID,BCL2 and BCL6 proteins in DLBCL tissues were detectd by immunohistochemical staining.Then to analyze the relationship between the expression of AID and clinical features of patients,the correlation between AID with BCL2 or BCL6 protein,and the survival and prognosis of patients.To detect AID mRNA in 4 DLBCL cell lines and peripheral blood mononuclear cells(PBMC)by the method of RTQ-PCR.Results(1)In the HBsAg(+)DLBCL group,the positive expression rate of AID protein was higher than that of HBsAg(-)group(86.7% VS 64.7%,P=0.032),(2)There were no significant relationship between expression of AID protein in DLBCL and clinical features(age,gender,immunological subtype,disease stage,international prognostic index(IPI score),tumor diameter,lactate dehydrogenase(LDH)level),(3)The expression of AID protein was correlated with BCL6(P<0.001)and was not associated with that of BCL2,(4)Amomg 69 patients with complete follow-up data,the 3-year cumulative survival rates were lower in the AID(+)group than in the AID(-)group(66.3% VS 68.2%,P=0.805)and that was also lower among non-GCB subtype of DLBCL(48.1% VS 80.0%,P=0.046),but among GCB subtype,there was no statistically significant difference between AID(+)group and AID(-)group(82.4% VS 77.8%,P=0.922),(5)Univariate survival analysis revealed that HBsAg(+),AID/HBsAg co-positive,immunological subtype,and IPI score were factors for poor prognosis in patients with DLBCL.Also,multivariate COX regression analysis indicated that AID/HBsAg co-positive,immunological subtype,and IPI score were independent factors for poor prognosis in patients with DLBCL,(6)The expression of AID mRNA was different in four of DLBCL cell lines.Except for OCI-ly8 cells,the others were significantly higher than that in normal human peripheral blood B cells(PBMC)(P<0.05).Conclusion(1)AID protein is highly expressed in HBV-associated DLBCL and is related to poor prognosis,particularly in non-GCB subtype,which deserving further exploration of its underlying mechanism and the role of AID in the development and progression of HBV-associated DLBCL.(2)The expression AID is correlated with that of BCL6 protein in DLBCL.