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Related Experiment Video

Updated: Jul 4, 2026

Methods to Enable Spatial Transcriptomics of Bone Tissues
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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
PubMed
Summary

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Paired single cell analysis reveals chemotherapy resistance in osteosarcoma.

Cancer drug resistance (Alhambra, Calif.)·2026

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.
Keywords:
cholesterol metabolismconsensus clusteringmetabolic subtypingosteosarcomaoxidative phosphorylationredox homeostasissingle-cell RNA sequencingtumor microenvironment

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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.