ABSTRACT
Burkitt lymphoma (BL) is an aggressive B cell lymphoma characterized by the reciprocal translocation of the c-Myc gene with immunoglobulin genes. Recently, MYC has been shown to maintain the neoplastic state via the miR-17-92 microRNA cluster that suppresses chromatin regulatory genes and the apoptosis regulator Bim. However, the expression and prognostic impact of miR-17-92 members in pediatric BL (pBL) are unknown. Therefore, we investigated miR-17, miR-19a, miR-19b, miR-20, and miR-92a expression and prognostic impact in a series of 41 pBL samples. In addition, Bim protein expression was evaluated and compared to miR-17, miR-19a, miR-19b, miR-20, and miR-92a levels and patient outcomes. The expression of miR-17-92 members was evaluated by qPCR and Bim protein by immunohistochemistry. Log-rank test was employed to assess prognostic impact. We found that upregulated expression of miR-17 and miR-20a correlates with lack of pro-apoptotic Bim expression. Patients bearing tumors with upregulated miR-17 displayed decreased overall survival (OS), and multivariate analysis revealed that miR-17 was a significant predictor of shortened OS. Using hairpin inhibitors, we showed that inhibition of miR-17 resulted in enhanced Bim expression in a BL cell line overexpressing the miR-17-92 cluster. Our results describe for the first time miR-17, miR-19a, miR-19b, miR-20a, and miR-92a expression profiles in pBL. The prognostic impact of miR-17 should be validated in a larger series, and may provide new therapeutic avenues in the era of anti-miRNA therapy research. Additional functional studies are further required to understand the specific role of miR-17-92 cluster members in BL.
Subject(s)
Burkitt Lymphoma/diagnosis , Burkitt Lymphoma/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Adolescent , Burkitt Lymphoma/metabolism , Child , Child, Preschool , Cluster Analysis , Female , Follow-Up Studies , Humans , Male , MicroRNAs/biosynthesis , Prognosis , RNA, Long NoncodingABSTRACT
A detecção precoce do câncer de mama (CM) é um fator de reconhecida importância no tratamento e prognóstico das pacientes, e as metástases para os linfonodos axilares (MLA) são os preditores mais importantes do seu prognóstico. A partir de um estudo caso-controle com 306 carcinomas ductais infiltrantes (CDI), foi construido um modelo preditivo da ocorrência de MLA em pacientes com CM (casos: CDI com MLA; controles: CDI sem MLA). Foram estudadas variáveis relacionadas às pacientes e ao tumor (características macro e microscópicas e marcadores tumorais). Na análise bivariada, algumas variáveis se associaram estatisticamente com o desfecho em questão, porém, na regressão logística não condicional, somente as seguintes variáveis foram fatores preditivos independentes: idade da paciente, tamanho do tumor, pleomorfismo nuclear, invasão vascular e/ou linfática (IV/IL) e o termo de interação tamanho do tumor e idade da paciente, onde o tamanho do tumor só foi fator preditivo em pacientes, com 60 anos ou mais. De acordo com os resultados deste estudo somente as variáveis idade da paciente, tamanho do tumor, pleomorfismo nuclear e IV/IL foram fatores preditivos para a ocorrência de MLA. Tanto os receptores hormonais quanto os marcadores tumorais estudados (c-erbB-2, catepsina D, MIB-1, PCNA e p53) não se mostraram importantes para predizer o desfecho em estudo, tanto na análise bivariada quanto na análise multivariada.
