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Analysis of Immune Gene Expression Subtypes Reveals Osteosarcoma Immune Heterogeneity
Ben Wan1, Renxian Wang1, Jingjun Nie1
1Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Traumatology and Orthopaedics, Beijing JiShuiTan Hospital, Beijing 100035, China.
Background:
Osteosarcoma (OS) patients have a poor response to immunotherapy due to the sheer complexity of the immune system and the nuances of the tumor-immune microenvironment. Methodology. To gain insights into the immune heterogeneity of OS, we identified robust clusters of patients based on the immune gene expression profiles of OS patients in the TARGET database and assessed their reproducibility in an independent cohort collected from the GEO database. The association of comprehensive molecular characterization with reproducible immune subtypes was accessed with ANOVA. Furthermore, we visualized the distribution of individual patients in a tree structure by the graph structure learning-based dimensionality reduction algorithm.
Results:
We found that 87 OS samples can be divided into 5 immune subtypes, and each of them was associated with distinct clinical outcomes. The immune subtypes also demonstrated widely different patterns in tumor genetic aberrations, tumor-infiltrating, immune cell composition, and cytokine profiles. The immune landscape of OS uncovered the significant intracluster heterogeneity within each subtype and depicted a continuous immune spectrum across patients.
Conclusion:
The established five immune subtypes in our study suggested immune heterogeneity in OS patients and may provide optimal individual immunotherapy for patients exhibiting OS.
Insights
Osteosarcoma patients were classified into five immune subtypes, revealing significant heterogeneity. This discovery may enable personalized immunotherapies for osteosarcoma (OS) by understanding distinct tumor-immune microenvironments.
Area of Science:
- Immunology
- Oncology
- Bioinformatics
Background:
- Osteosarcoma (OS) exhibits poor immunotherapy response due to complex tumor-immune microenvironments.
- Understanding immune heterogeneity is crucial for improving OS treatment outcomes.
Purpose of the Study:
- To identify and validate distinct immune subtypes in osteosarcoma patients.
- To explore the relationship between immune subtypes and clinical outcomes, genetic aberrations, and immune cell profiles.
Main Methods:
- Clustering of patients based on immune gene expression profiles from TARGET and GEO databases.
- Assessed reproducibility and association with molecular characteristics using ANOVA.
- Utilized graph structure learning for dimensionality reduction and patient distribution visualization.
Main Results:
- Identified five reproducible immune subtypes in 87 OS samples, each linked to different clinical outcomes.
- Observed distinct patterns in genetic aberrations, immune cell infiltration, and cytokine profiles across subtypes.
- Revealed significant intracluster heterogeneity and a continuous immune spectrum among OS patients.
Conclusions:
- The five identified immune subtypes highlight the significant immune heterogeneity in osteosarcoma.
- These subtypes offer a potential framework for developing individualized immunotherapy strategies for OS patients.
