Systems biology-based analysis highlights altered processes that impact overall survival of Ewing Sarcoma patients
Ewing’s sarcoma, Autophagy, DNA damage response, Immune response, Hippo pathway
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 fator EWSR1-FLI that drives metabolic reprogramming in ES. The ES survival rate has increased at the cost of high toxicity that limits survival rates and causes significant morbidity. Therefore it is crucial to identify and obtain a complete 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.