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Related Experiment Video

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Single-Cell Transcriptomic Analysis of Chemotherapy-Induced Changes in Osteosarcoma With a Pyroptosis-Related

Tao Jin1,2, Lei Dong3, Wang Kai4

  • 1Department of Orthopaedic Oncology Surgery, Beijing Jishuitan Hospital, Capital Medical University, National Center for Orthopaedics, Beijing, China.

Journal of Cellular and Molecular Medicine
|March 28, 2026
PubMed
Summary

Chemotherapy alters osteosarcoma cell populations and activates programmed cell death via pyroptosis. A new Pyroscore model predicts better survival, offering insights for personalized osteosarcoma treatment.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Osteosarcoma, a primary bone cancer, faces treatment hurdles due to its microenvironment and chemoresistance.
  • Understanding chemotherapy's cellular and molecular effects is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate chemotherapy-induced changes in osteosarcoma cell subpopulations and molecular pathways.
  • To develop and validate a prognostic model for osteosarcoma based on pyroptosis-related genes.

Main Methods:

  • Single-cell RNA sequencing was used to analyze chemotherapy effects on cell populations.
  • Differential gene expression, pathway enrichment, and machine learning algorithms were employed.
  • A predictive model (Pyroscore) was developed using pyroptosis genes (BAK1, CASP1, CASP5, CASP6).

Main Results:

  • Chemotherapy altered immune and stromal cell proportions, increasing osteoclasts and decreasing T/NK cells.
  • The pyroptosis pathway was significantly upregulated in tumor cells, indicating chemotherapy-induced programmed cell death.
  • Metabolic pathways, including sulphur and fatty acid metabolism, were notably inhibited.
  • The Pyroscore model showed strong prognostic value, with higher scores linked to improved survival.

Conclusions:

  • Chemotherapy significantly impacts osteosarcoma cell composition and the tumor microenvironment.
  • Pyroptosis pathway activation is a key mechanism in chemotherapy response.
  • The Pyroscore model offers a novel tool for predicting osteosarcoma patient prognosis and guiding personalized therapy.