Background: Osteosarcoma is the most frequent bone cancer in children and young adults. Histological response and control of primary metastases are the main prognostic clinical factors, but are insufficient to identify the ∼30% of hard-to-treat patients and are not predictive of the response to combinations of chemotherapies or biological treatments. Our aim was to evaluate if circulating proteomic analyses could predict tumor progression. Methods: 88 plasma samples from newly diagnosed patients with osteosarcoma in the OS2006 trial were sequenced using the OLINK Explore panel (3072 proteins) and 88 more coming from the SARCOME13 trial will be used as a validation cohort. Results: Principal component analysis defined co-circulating proteins associated to critical biological pathways involved in osteosarcoma oncogenesis, such as cell adhesion, cell survival/growth, bone formation and extracellular matrix organization. Cox survival analysis associated circulating bone formation pathway with OS(HR=1.10 [1.03;1.17], p=0.006) and PFS(HR=1.12 [1.05;1.19], p=<0.001). These circulating pathways were also associated with presence of metastases at diagnosis (odd ratio = 1.33 [1.12;1.72], p=0.006). These results are being validated on SARCOME13 data. Conclusion: Proteomic plasma markers quantification in patients with osteosarcoma at diagnosis capture a biological signal significantly associated to prognosis and the presence of metastasis at diagnosis.

Citation Format: Baptiste Audinot, Damien Drubay, Maria Eugenia Da Costa, Gael Moquin Beaudry, Marta Jimenez, Birgit Geoerger, Nathalie Gaspar, Samuel Abbou, Antonin Marchais. Plasma circulating proteomic markers are associated with metastatic spread and outcome in osteosarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A043.