RESUMO
OBJECTIVES: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). DESIGN AND METHODS: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates. RESULTS: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB) type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS) and progression-free survival (PFS) in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. CONCLUSION: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP.
RESUMO
The aberrant expression of microRNAs (miRs) has a significant impact on the biological characteristics of lymphocytes, and is important in the pathogenesis of diffuse large B-cell lymphoma (DLBCL). It has been demonstrated, using miR profiling and detecting distinct miR signatures, that certain miRs may accurately distinguish different subtypes and prognostic classifications of DLBCL, as well as distinguish DLBCL from other more indolent lymphomas, including follicular lymphoma. miRs are excellent biomarkers for cancer diagnosis and prognosis. In DLBCL, specific miR expression profiles in the tissues of patients are associated with prognosis and clinical outcome. Over the past decade, there has been substantial investigation concerning the pathogenetic, diagnostic and prognostic roles of miRs in DLBCL. The aim of the present review is to describe the aberrant expression of miRs in DLBCL, and the functions, potential clinical use and possible therapeutic targets of miRs in this disease.
RESUMO
OBJECTIVE: To investigate the expression and prognostic value of miR-224 expression in patients with diffuse large B-cell lymphoma (DLBCL) who underwent R-CHOP. MATERIALS AND METHODS: RT-PCR was used to determine the relative expression of miR-224, in 258 DLBCL patients and 40 normal lymphoid tissue specimens. RESULTS: MiR-224 expression in DLBCL patients was significantly down-regulated compared to that in negative controls (p < 0.05). The 5-year progression-free survival and overall survival rates were significantly higher in the high-expression level group compared to the low-expression level group (p < 0.05). CONCLUSIONS: MiR-224 expression level is implicated as a prognostic marker for DLBCL patients treated with R-CHOP.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Biomarcadores Tumorais/genética , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do Tratamento , Vincristina/administração & dosagem , Adulto JovemRESUMO
miRNAs are non-coding RNA molecules; their deregulations may contribute to cancer pathogenesis. However, the mechanisms of how miRNA dysfunction contributes to the lymphomagenesis of diffuse large B-cell lymphoma (DLBCL) are not well established. In this study, we analyzed the expression of miR-224 in four DLBCL cell lines and 168 patients' specimens. We found that the expression of miR-224 in DLBCL was down-regulated compared with normal B-cell but was not statistically different between the germinal center B-cell-like-type and the activated B-cell-like-type. Using bioinformatics prediction and luciferase report assays, we demonstrated that miR-224 directly down-regulated CD59 expression by binding to its 3'-untranslated region. We also used immunohistochemical staining of CD59 in human DLBCL specimens and analyzed the relationship between the expression of miR-224, CD59 and the overall/progress-free survival of DLBCL patients who were uniformly treated with rituximab,cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). We found that miR-224 may contribute to DLBCL pathogenesis. Most importantly, the expression of miR-224 and CD59 can predict the response and outcome of DLBCL patients treated with R-CHOP.
