RESUMO
Glioma has a poor prognosis due to its rapid overgrowth, diffuse invasion, and chemotherapy resistance. The improvements in clinical outcome are still limited and the identification of novel biomarkers involved in the progression of gliomas is still under critical demands. Amino acid ADP-ribosyltransferase 1 (ART1) is an enzyme that catalyzes the mono-ADP-ribosylation, a reversible post-translational modification. For example, the mono-ADP-ribosylation of transcription factors can affect their binding to target gene promoters. However, the functional significance of ART1 in glioma has not been reported. We collected 107 glioma cases from Qianfoshan Hospital and Yidu Central Hospital of Weifang between April 2008 and September 2015 to analyze the prognosis value of ART1 in gliomas. RT-qPCR analysis showed that the expression level of ART1 mRNA in glioma tissues was 4-fold higher than that in normal brain tissues. According to the immunohistochemical staining results, 44 patients (41.1%) were categorized as ART1 positive (≥ 20% of stained glioma cells), while the other 63 patients (58.9%) categorized as ART1 negative (< 20% of stained glioma cells). Moreover, the mean percentage of ART1-positive cells was 43.7%, 53.6% and 64.2% in WHO grade II, III and IV specimens, respectively. Through univariate and multivariate analyses, we identified ART1 as an independent prognostic factor. We also found that ART1 overexpression in U251 glioblastoma cells could significantly decrease the susceptibility to vincristine, one of tubulin-targeted drugs, which is widely used in clinical treatment for glioma. Taken together, we propose that up-regulation of ART1 expression is associated with the aggressiveness of glioma.
Assuntos
ADP Ribose Transferases/genética , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/enzimologia , Glioma/genética , ADP Ribose Transferases/metabolismo , Adulto , Idoso , Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Análise de Sobrevida , Tubulina (Proteína)/metabolismo , Vincristina/farmacologiaRESUMO
In order to understand the pathogenic factors that initiate the processes of Alzheimer's disease (AD), a method of inference of multiple differential modules (iMDM) to conduct analysis was performed on the gene expression profile of AD. A total of 11,089 genes and 588,391 interactions were gained based on the gene expression profile and protein-protein interaction network. Subsequently, three differential co-expression networks (DCNs) were constructed with the same nodes but different interactions, and eight multiple differential modules (M-DMs) were identified. Furthermore, by performing Module Connectivity Dynamic Score to quantify the change in the connectivity of component modules, two M-DMs were identified: Module 1 (P=0.0419) and 2 (P=0.0419; adjusted, P≤0.05). Finally, hub genes of MDH1, NDUFAB1, NDUFB5, DDX1 and MRPS35 were gained via topological analysis conducted on the 2 M-DMs. In conclusion, the method of iMDM was suitable for conducting analysis on AD. By applying iMDM, 2 M-DMs were successfully identified and the MDH1, NDUFAB1, NDUFB5, DDX1 and MRPS35 genes were predicted to be important during the occurrence and development of AD.