Molecular markers of proliferation, DNA repair, and immune infiltration defines high-risk subset of resectable retroperitoneal sarcomas

Introduction: For retroperitoneal sarcomas (RPS), aggressive surgical resection offers the only chance for a cure; however, 5-year survival remains below 65%. Therefore, there is a critical need to identify drivers of poor clinical outcomes. Materials and methods: To identify biomarkers of tumors likely to recur following curative intent resection, we performed genomic and transcriptomic sequencing for 47 and 34 patients, respectively, with non-metastatic RPS at a single, high-volume sarcoma center. Results: At the DNA level, alterations in TERT were associated with poor disease-free survival (DFS) and overall survival (OS). Increased RNA expression of gene sets related to growth signaling and DNA repair were associated with poor DFS and OS. Infiltration of CD8⁺ T-Cells and activated dendritic cells were associated with poor DFS and OS. Conclusion: These findings may help to better identify and treat non-metastatic, high-risk RPS.