Tumor immune microenvironment-associated prognostic and mifamurtide-response gene signatures for localized osteosarcoma: a correlative study of the ISG/OS2 trial
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View abstract on PubMed
Summary
This summary is machine-generated.A novel 21-gene signature predicts osteosarcoma risk and survival, independent of mifamurtide treatment. A separate 31-gene signature identifies response to mifamurtide, revealing key tumor-immune interactions.
Area Of Science
- Oncology
- Immunology
- Genomics
Background
- Osteosarcoma is a rare bone cancer with significant unmet needs in risk stratification and treatment personalization.
- The tumor immune microenvironment (TME) plays a crucial role in cancer progression and response to therapy.
- Mifamurtide is an immunotherapy agent used in combination with chemotherapy for osteosarcoma.
Purpose Of The Study
- To identify prognostic gene signatures based on TME profiling in localized osteosarcoma patients.
- To evaluate these signatures in all patients and specifically in those treated with mifamurtide.
- To explore the relationship between TME, gene expression, and treatment outcomes in osteosarcoma.
Main Methods
- RNA extracted from pre-treatment osteosarcoma tissues of 62 patients was analyzed using the PanCancer Immune profiling panel.
- Patients were stratified into P-glycoprotein (Pgp)-positive (chemotherapy + mifamurtide) and Pgp-negative (chemotherapy alone) groups.
- Statistical analyses included univariate Cox regression, ROC curve analysis, and CIBERSORTx gene deconvolution.
Main Results
- A 21-gene signature robustly stratified patients into high-risk (47% 5-year OS) and low-risk (92% 5-year OS) groups (p=3e-06).
- The low-risk TME was enriched in CD8 T-cells, T-regs, and NK cells, while diminished in CD4 T-cells.
- A 31-gene signature associated with mifamurtide treatment independently predicted overall survival (OS) and event-free survival (EFS).
Conclusions
- A validated 21-gene signature prognostic for osteosarcoma TME has been identified, irrespective of mifamurtide treatment.
- A distinct 31-gene signature related to mifamurtide treatment efficacy was also developed.
- These findings highlight the importance of tumor-immune interactions in osteosarcoma progression and treatment response.
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