Análise baseada em biologia de sistemas destaca processos alterados que afetam a sobrevida geral de pacientes com sarcoma de Ewing ; Systems biology-based analysis highlights altered processes that impact overall survival of Ewing sarcoma patients

Ewing’s Sarcoma (ES) is a highly aggressive disease and the second most frequent pediatric bone neoplasm. The ES hallmark is the presence of the aberrant transcription factor EWSR1-FLI that drives metabolic reprogramming. Therapeutic procedures have partially increased ES survival rate, but still present high toxicity and cause significant morbidity. To suggest more efficient therapeutic strategies, a more comprehensive understanding of the pathways that impact ES survival for development of novel diagnostics and therapeutic strategies. Here, we identified differences at the transitional level between ES patients with short-term survivors (STS) and long-term survivors (LTS) based on transcriptional data available in three public datasets, applying the transcriptogram analysis. Three differentially expressed clusters commons across the cohorts analyzed were identified. Processes related to DNA damage response and repair, immune response, apoptosis and autophagy were dysregulated between the STS and LTS groups. Furthermore, the functional enrichment of the common genes between three clusters and ES regulons highlight the upregulation of the Hippo pathway in STS patients. Our analysis suggests that different processes may be guiding the outcome of ES patients in an integrated way and may contribute to the diversity of phenotypes driven by the EWSR1-FLI1 expression fluctuation. ; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES ; O Sarcoma de Ewing (SE) é uma doença altamente agressiva e a segunda neoplasia óssea pediátrica mais frequente. A marca registrada do SE é a presença do fator de transcrição aberrante EWSR1-FLI que impulsiona a reprogramação metabólica. Os procedimentos terapêuticos aumentaram parcialmente a sobrevida do SE, mas ainda apresentam alta toxicidade e causam morbidade significativa. Para sugerir estratégias terapêuticas mais eficientes, é necessário um entendimento mais abrangente das vias que impactam a sobrevivência do SE para o desenvolvimento de novos diagnósticos e ...