The Relevance Of MiR-222and MiR-125b To Clinicopathological Characteristics And Prognosis Of Diffuse Large B-cell Lymphoma

Part IClinical analysis of Diffuse large B-cell lymphomaObject： To study the clinicopathological characteristics, treatment, short-termtherapeutic effect and its affecting factors in Diffuse large B-cell lymphoma (DLBCL)patients. To determine the rate of hepatitis B virus (HBV) infection and reactivationof DLBCL patients, and investigate their characteristics, treatments and outcomes.Methods: Retrospective analysis of the clinical data of DLBCL patients, who werediagnosed in our hospital between2004and2012. Then investigate theclinicopathological characteristics (sex, age, stage, serum lactate dehydrogenase level,B symptoms, ECOG, primary site, number of extranodal sites involved, IPI score,Hans typing, Ki-67index and bulky disease), treatment and short-term therapeuticeffect, and the rate of HBV infection and reactivation of DLBCL patients, as well asthe treatments and outcomes of DLBCL patients with HBV infection.Results:1.The median age of the88DLBCL patients was48.5years (13-84years),and the male-to-female ratio was1.32:1. There were75%patients in Ⅲ-Ⅳ stage,38.6%with B symptoms, and47.7%with elevated LDH at diagnosis. Seventeenpercent patients were presence of bulky disease and5.7%patients had bone marrowinvolved. The percentage of patients in low, low-intermediate, high-intermediate andhigh risk groups were38.6%、33%、14.8%and13.6%, respectively.2.According to Hans’ algorithm,30.4%of56DLBCL patients were classi ed asGCB subtype, and69.6%as non-GCB subtype. In59DLBCL patients who detectedKi-67index,35.6%patients were with Ki-67index≥80%.3. In88DLBCL patients,47.7%were primary nodal DLBCL and52.3%wereprimary extranodal DLBCL(E-DLBCL). The most common primary extranodal siteswere gastrointestinal tract and Walderyer’s ring, accounting for39.1%and15.2%ofthe primary E-DLBCL, respectively.4. In88DLBCL patients,65.9%were treated with chemotherapy only,30.7%patients confirmed by pathology after surgical excision and then receivedchemotherapy. Thirty-three percent patients treated with R-CHOP/R-ECHOP regimen, 55.7%with CHOP/E-CHOP/E-POCH regimen, and11.3%with both R-CHOP andCHOP regimens.5.All patients with the rates of complete remission (CR), partial remission (PR), stabledisease (SD) and progressive disease (PD) were63.6%,21.6%,5.7%and9.1%,respectively. The effective factors of CR rate were unfavourable IPI (3-5), Ⅲ-Ⅳ stage,elevated LDH and non-GCB subtype.6. Seventy-three DLBCL patients have detected the HBV. HBsAg-positive rate was35.6%, previous HBV infection rate was17.8%. The rates of HBV reactivation in theHBsAg-positive and HBsAg-negative with HBcAb-positive patients were15.4%, and7.7%. Four of five HBV reactivation DLBCL patients were treated with R-CHOPregimen, and none of them received preventive antiviral treatment. However, allpatients were better through liver protection and nucleoside or nucleotide analogue(NA) treatment.Conclusion: DLBCL is the most common type of non-Hodgkin lymphoma(NHL),and displays heterogeneous clinical features. Gastrointestinal DLBCL was the mostcommon primary E-DLBCL, followed by Walderyer’s ring DLBCL. The effectivefactors of CR rate were unfavourable IPI (IPI3-5), Ⅲ-Ⅳ stage, elevated LDH andnon-GCB subtype. The incidence of HBV in DLBCL is higher than that in healthypeople. Rituximab could increase the rate of HBV reactivation. The DLBCL patientswith HBsAg-positive need preventive antiviral treatment, and HBsAg-negative withHBcAb-positive patients should be highly alert to HBV reactivation. Part IIThe relevance of miR-222and miR-125b to clinicopathologicalcharacteristics and prognosis of Diffuse large B-cell LymphomaPurpose: The heterogeneity of diffuse large B-cell lymphoma (DLBCL) impeded theassessment of curative effect and prognosis of patients, so new biomarkers should bedeveloped to predict the survival of the patients accurately. The aim of the presentstudy was to investigate the expression of miR-222and miR-125b in DLBCL, and therelevance of the two micro-RNAs to clinicopathological characteristics and prognosisof DLBCL.Methods: Retrospective analysis of the clinical data of41DLBCL patients. Theexpression of miR-222and miR-125b in FFPE samples of DLBCL patients and theircontrols were evaluated by quantitative real-time PCR.Results: Ten patients (24.4%) were classi ed as GCB subtype, and31patients(75.6%) as non-GCB subtype. The expression levels of miR-222in DLBCL wassignificantly higher than that in reactive hyperplasia lymphoid nodes, especially innon-GCB type, but miR-125b did not show no significant difference between twogroups. The patients with high miR-222expression achieved a lower completeremission rate (53.8%vs.86.7%, P=0.033), and multivariate analysis revealed thathigh miR-222expression was an independent prognostic factor for progression-freesurvival (P=0.027; HR5.084). Low-expression of miR-125b was associated withhigh IPI score (IPI>2, P=0.031), high Ki-67index (Ki-67≥80%, P=0.015), elevatedLDH (P=0.028) and bulky disease (P=0.018).Conclusion:High miR-222expression is associated with poor PFS, which indicatesthat miR-222might be a new prognostic biomarker for DLBCL. Low-expression ofmiR-125b was associated with some negative factors of DLBCL, so miR-125b mayfunction as a tumor suppressor, yet the exact role of the two miRNAs in thepathogenesis of DLBCL should be investigated further.