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Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
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Inflammation-driven prognostic model and immune landscape profiling in osteosarcoma.

Rongquan Zhang1, Xueliang Zhou1, Chenxiao Shen2

  • 1Zhejiang Province People's Hospital Haining Hospital, Jiaxing, China.

Discover Oncology
|November 7, 2025
PubMed
Summary

A new 11-gene signature predicts osteosarcoma patient survival by analyzing inflammation. This inflammation-related risk model offers a prognostic tool and suggests therapeutic targets, including potential repurposing of Temozolomide.

Keywords:
Immune infiltrationInflammation-related genesOsteosarcomaRisk scoring modelSingle-cell RNA sequencing

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Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Osteosarcoma (OS) is a primary bone cancer in young adults with poor prognosis, especially in metastatic cases.
  • Chronic inflammation in the tumor microenvironment drives OS progression and immune evasion.
  • Existing prognostic models often lack inflammation-related molecular features.

Purpose of the Study:

  • To develop a novel prognostic model for osteosarcoma based on inflammation-related genes.
  • To investigate the relationship between tumor inflammation, immune infiltration, and patient survival.
  • To identify potential therapeutic targets and drug repurposing opportunities for OS.

Main Methods:

  • Utilized bulk RNA-seq data from TCGA for osteosarcoma patients.
  • Defined an inflammation gene set and employed LASSO and Cox regression to identify prognostic genes.
  • Constructed and validated an 11-gene risk-scoring model and a nomogram.
  • Analyzed single-cell RNA-seq data to map inflammation gene expression across cell types.
  • Assessed immune infiltration and performed pathway enrichment analyses.

Main Results:

  • The 11-gene signature stratified patients into high and low risk groups with significantly different overall survival (p < 0.001).
  • The prognostic model achieved high discriminative ability (AUCs 0.808-0.879 at 1-5 years).
  • Single-cell analysis revealed specific immune cell enrichment, and low-risk tumors showed higher immune infiltration and activity.
  • Molecular docking suggested Temozolomide as a potential drug repurposing candidate targeting TERT.

Conclusions:

  • Developed a novel, inflammation-based prognostic tool for osteosarcoma.
  • Elucidated the complex interplay between tumor inflammation and immune microenvironment in OS.
  • Identified potential therapeutic strategies and drug repurposing candidates for osteosarcoma treatment.