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Updated: Jul 4, 2026
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Methods to Enable Spatial Transcriptomics of Bone Tissues
Published on: May 3, 2024
Transcriptome-Inferred metabolic subtypes define prognostic and immune ecosystems in osteosarcoma at single-cell
Li Hu1, Dingsheng Zhang2, Boyang Wang3
1Familial & Hereditary Cancer Center, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China.
Frontiers in Pediatrics
|July 3, 2026
Summary
Osteosarcoma metabolism varies significantly by cell type. New subtypes reveal distinct origins and survival outcomes, guiding targeted therapies for this bone cancer.
Area of Science:
- Oncology
- Metabolic Engineering
- Genomics
Background:
- Osteosarcoma displays significant metabolic heterogeneity, but current classifications lack cellular origin details.
- Existing metabolic pathway analyses are often limited in scope.
Purpose of the Study:
- To identify distinct metabolic subtypes of osteosarcoma based on integrated transcriptomic data.
- To attribute these subtypes to specific cellular origins within the tumor microenvironment.
- To correlate metabolic subtypes with clinical outcomes for improved risk stratification.
Main Methods:
- Integrated bulk transcriptomes from 157 osteosarcoma tumors.
- Quantified pathway activity using single-sample gene set enrichment analysis (ssGSEA).
- Performed consensus clustering to define metabolic subtypes and single-cell RNA sequencing to determine cellular origins.
Main Results:
- Identified three stable metabolic subtypes: Cholesterogenic (C1), Redox-Catabolic (C2), and OXPHOS-Active (C3).
- C2 subtype showed favorable survival (90.8% 3-year OS), while C1 (60.0%) and C3 (61.9%) had adverse outcomes.
- C1 signatures originated from stromal/mesenchymal cells, C2 from immune cells, and C3 from malignant tumor cells.
Conclusions:
- Osteosarcoma metabolic subtypes are linked to specific cell-of-origin signatures.
- This cell-aware classification enables niche-resolved risk stratification.
- Findings support the development of cell-specific therapeutic strategies for osteosarcoma.
