Evaluation of tumorous LCP1 and ADPGK as predictive biomarker for immune-related adverse events in bone and soft tissue sarcomas treated with anti-PD-1 and anti-PD-L1 antibodies

Abstract

Immune checkpoint inhibitor (ICI) have been utilized in bone and soft tissues sarcoma patients under multiple circumstances in combination with surgeries and chemotherapy. Regretfully, immune-related adverse events (irAE) increases as the usage of ICI increases. Since a large portion of bone and soft tissues sarcoma patients gain long survival times after successful removal of the tumors which makes clinicians to avoid regimens that causes adverse events, especially lifetime irAE. Hence, predicting the development of irAE are of special significance for utilizing ICI in bone and soft tissues sarcoma patients. We have retrospectively stained tumorous LCP1 and ADPGK, two biomarkers previously reported to predict ICI induced irAE, with surgical removed, formalin-fixed and parrffin-embedded samples in a cohort of 56 bone and soft tissues sarcoma patients. We observed that the most common irAE in bone and soft tissues sarcoma patients received ICI is hyperglycemia and high grade irAE happens predominately in patients over 30 years old. Immunochemistry revealed that both LCP1 and ADPGK were elevated in tumorous tissues of patients developed irAE and bivariate-model of LCP1 and ADPGK severs as a better biomarker in comparison to LCP1 or ADPGK alone in the entire cohort. In osteosarcoma, LCP1 alone exhibited an outstanding predication value with an AUC of 0.9244 (P value of 0.0013 and a 95% CI of 0.8178 to 1.000). LCP1 and ADPGK bivariate-model serves as a promising biomarker for predicting ICI induced irAE in bone and soft tissues sarcoma patients while LCP1 alone works better in bone malignancy especially in osteosarcoma.