Circulating Exosomal PD-L1 at Initial Diagnosis Predicts Outcome and Survival of Patients with Osteosarcoma

Abstract Purpose: It is difficult to predict prognosis of patients with osteosarcoma at initial diagnosis due to lack of efficient prognostic parameters. We evaluated the relationship between level of circulating serum exosomal PD-L1 (Sr-exosomal PD-L1) at initial diagnosis and oncologic outcome during the follow-up. Experimental Design: Sixty-seven patients with newly diagnosed osteosarcoma were prospectively recruited. Fasting blood was collected and exosome isolation was performed using ultracentrifugation method. Evaluation of Sr-exosomal PD-L1 was performed respectively by immunogold labeling and ELISA method. Correlation between level of Sr-exosomal PD-L1 at initial diagnosis and clinical risk factors was assessed. Results: Mean follow-up was 46.7 months. Two-year and 5-year overall survival (OS) rates were respectively 96.9% and 62.5%. Two-year and 5-year disease-free survival (DFS) rates were respectively 85.0% and 31.4%. Results revealed a significantly positive association between high PD-L1 cargo of circulating exosomes and clinicopathologic disease markers such as pulmonary metastasis, multiple metastasis, and death. Patients who died of disease at final follow-up had higher level of Sr-exosomal PD-L1 at initial diagnosis, which compared with patients who were still alive at last follow-up. Patients in group of ≥14.23 pg/mL Sr-exosomal PD-L1 at initial diagnosis had inferior DFS compared with patients in group of <14.23 pg/mL at initial diagnosis. Patients in group of ≥25.96 pg/mL at initial diagnosis had poor OS compared with patients in group of <25.96 pg/mL at initial diagnosis. Conclusions: Use of liquid biopsy of circulating exosomal PD-L1 at initial diagnosis provides a robust means of predicting prognosis for patients with a newly diagnosed osteosarcoma.