1. Peripheral Soluble Immune Checkpoint-Related Proteins Were Associated with Survival and Treatment Efficacy of Osteosarcoma Patients, a Cohort Study.
- Author
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Li, Binghao, Wang, Qinchuan, Luo, Yihong, Wang, Sicong, Pan, Sai, Zhao, Wenting, Ye, Zhaoming, and Wu, Xifeng
- Subjects
OSTEOSARCOMA ,MEDICAL logic ,PEARSON correlation (Statistics) ,PREDICTION models ,T-test (Statistics) ,STATISTICAL significance ,RESEARCH funding ,IMMUNOTHERAPY ,MULTIPLE regression analysis ,CANCER patients ,TREATMENT effectiveness ,MULTIVARIATE analysis ,MANN Whitney U Test ,CHI-squared test ,DESCRIPTIVE statistics ,METASTASIS ,LOG-rank test ,KAPLAN-Meier estimator ,LUNG tumors ,STATISTICS ,PROGRESSION-free survival ,DATA analysis software ,IMMUNE checkpoint proteins ,OVERALL survival ,BIOMARKERS ,PROPORTIONAL hazards models ,DISEASE progression - Abstract
Simple Summary: Osteosarcoma is one of the most lethal bone tumors worldwide. Immune checkpoint blockades have achieved significant success in solid tumors; however, their role in osteosarcoma remains obscure. Therefore, we aim to explore the clinical significance of soluble immune checkpoint-related proteins in osteosarcoma in this study. We identified four soluble immune checkpoint-related proteins as predictors of progress-free survival and lung metastasis-free survival of osteosarcoma patients. Our findings indicated that soluble immune checkpoint-related proteins could be promising biomarkers for the outcomes and immunotherapy of osteosarcoma. Background: The immune checkpoint blockade remains obscure in osteosarcoma (OS). We aim to explore the clinical significance of soluble immune checkpoint (ICK)-related proteins in OS. Methods: We profiled 14 soluble ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, CD28, CD80, CD137, CD27, and CTLA-4) in the plasma of 76 OS patients and matched controls. We evaluated the associations between the biomarkers and the risk of OS using unconditional multivariate logistic regression. The multivariate Cox model was utilized to develop the prediction model of OS. Immune subtypes were established from the identified biomarkers. Transcriptional data from GEO were analyzed to elucidate potential mechanisms. Results: We found that sTIM3, sCD137, sIDO, and sCTLA4 were significantly correlated with OS risk (all p < 0.05). sBTLA, sPDL2, and sCD27 were significantly associated with the risk of lung metastasis, whereas sBTLA and sTIM3 were associated with the risk of disease progression. We also established an immune subtype based on sBTLA, sPD1, sTIM3, and sPDL2. Patients in the sICK-type2 subtype had significantly decreased progression-free survival (PFS) and lung metastasis-free survival (LMFS) than those in the sICK-type1 subtype (log-rank p = 2.8 × 10
−2 , 1.7 × 10−2 , respectively). Interestingly, we found that the trend of LMFS and PFS in the subtypes of corresponding ICK genes' expression was opposite to the results in the blood (log-rank p = 2.6 × 10−4 , 9.5 × 10−4 , respectively). Conclusion: Four soluble ICK-related proteins were associated with the survival of OS patients. Soluble ICK-related proteins could be promising biomarkers for the outcomes and immunotherapy of OS patients, though more research is warranted. [ABSTRACT FROM AUTHOR]- Published
- 2024
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