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

Abstract

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. 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. 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. 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.