bioimagesUnknownhttps://www.ebi.ac.uk/biostudies/studies/S-BIAD1597bioimagesSpecimenImage analysisStudy ComponentorganisationBiosampleAssociationsImage acquisitionTamar GeigerSagi GordonLiat Fellus-AlyagorOfra GolaniVishnu MohanfalseProteomic landscape of Ewing sarcoma primary tumors and metastasesEwing sarcoma (EWS), a rare pediatric bone tumor, poses unique therapeutic challenges due to its distinct microenvironment and limited molecular understanding. To gain a comprehensive molecular and functional view of the tumors in their microenvironment, we performed a deep mass spectrometry-based proteomic analysis of 168 tumors from 72 patients from primary, relapsed, and metastatic tumors. Analysis of more than 10,000 proteins across patients revealed novel insights into cancer prognosis, chemo-resistance, and progression. We found ferroptosis inhibition as a potential mediator of EWS chemo-resistance and identified novel subclasses of EWS that link the tumor immune landscape with DNA damage repair, ubiquitin-related proteins, and patient prognosis. Validation by multiplexed immunofluorescence imaging confirmed the association between patient prognosis and tumor neutrophils, and association of macrophages and T-cells with better prognosis. These results suggest that immuno-oncological treatments might be efficacious for a subset of patients. Altogether, this comprehensive investigation provides valuable insights into the intricate biology of EWS, paving the way for developing novel therapeutic strategies.2025-12-25T00:00:00Z2026-01-18T16:58:03.868Z2025-01-28T06:54:34.58ZS-BIAD1597