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Updated: Jun 26, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Peripheral Soluble Immune Checkpoint-Related Proteins Were Associated with Survival and Treatment Efficacy of
Binghao Li1,2, Qinchuan Wang3,4,5, Yihong Luo4,5
1Department of Orthopedics, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
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.
Insights
Soluble immune checkpoint proteins are linked to osteosarcoma risk and patient outcomes. These proteins may serve as biomarkers for predicting prognosis and guiding immunotherapy in osteosarcoma (OS).
Area of Science:
- Immunology
- Oncology
- Biomarker Discovery
Background:
- The role of immune checkpoint blockade in osteosarcoma (OS) is not well understood.
- Investigating soluble immune checkpoint (sICK) proteins in OS plasma is crucial for understanding disease mechanisms and patient outcomes.
Purpose of the Study:
- To explore the clinical significance of 14 soluble immune checkpoint-related proteins in osteosarcoma patients.
- To identify potential biomarkers for predicting OS risk, metastasis, progression, and survival.
Main Methods:
- Plasma samples from 76 osteosarcoma patients and controls were analyzed for 14 soluble immune checkpoint proteins.
- Unconditional multivariate logistic regression and multivariate Cox models were used to assess biomarker associations and develop a prediction model.
- Immune subtypes were established, and transcriptional data were analyzed to explore underlying mechanisms.
Main Results:
- Four soluble immune checkpoint proteins (sTIM3, sCD137, sIDO, sCTLA4) significantly correlated with osteosarcoma risk.
- Specific sICK proteins (sBTLA, sPDL2, sCD27, sTIM3) were associated with lung metastasis and disease progression.
- An immune subtype (sICK-type2) defined by sBTLA, sPD1, sTIM3, and sPDL2 showed significantly worse progression-free survival and lung metastasis-free survival compared to sICK-type1.
Conclusions:
- Four soluble immune checkpoint-related proteins are significantly associated with osteosarcoma patient survival.
- Soluble immune checkpoint proteins show promise as biomarkers for predicting osteosarcoma outcomes and response to immunotherapy.
- Further research is warranted to validate these findings and explore their therapeutic implications.
