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Updated: Jan 13, 2026

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
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AGPAT3 Regulates Immune Microenvironment in Osteosarcoma via Lysophosphatidic Acid Metabolism

Shenghui Su1, Yu Zeng1, Jiaxin Chen1

  • 1JXHC Key Laboratory of Digital Orthopaedics, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, 330006, China.

Oncology Research
|January 8, 2026
PubMed
Abstract

Insights

Glycerolipid metabolism gene AGPAT3 impacts osteosarcoma prognosis and immune response. Targeting lysophosphatidic acid receptor 6 (LPAR6) signaling in tumor-associated macrophages (TAMs) offers new immunotherapy strategies for osteosarcoma.

Area of Science:

  • Oncology
  • Immunology
  • Metabolism

Background:

  • Glycerolipid metabolism is crucial in various cancers, but its role in osteosarcoma remains largely unexplored.
  • Understanding these metabolic pathways is key to identifying novel therapeutic targets for osteosarcoma.

Purpose of the Study:

  • To investigate the function of glycerolipid metabolism in osteosarcoma.
  • To identify key genes and pathways involved in osteosarcoma progression and immune evasion.

Main Methods:

  • Bioinformatics analysis of TARGET database and single-cell RNA sequencing data.
  • LASSO regression to identify prognostic glycerolipid metabolism genes.
  • Single-cell analysis and co-culture experiments to study tumor-associated macrophages (TAMs) and immune interactions.
  • Virtual screening for lysophosphatidic acid receptor 6 (LPAR6) inhibitors.

Main Results:

  • 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) and aldehyde dehydrogenase 7 family member A1 (ALDH7A1) identified as key prognostic genes; high AGPAT3 expression correlates with better survival.
  • AGPAT3 expression is linked to the tumor immune microenvironment, particularly TAMs.
  • AGPAT3 knockdown increases lysophosphatidic acid (LPA) levels, impairing T cell function via TAM LPAR6 signaling and altering cytokine secretion (IL-6, IL-10).
  • Dutasteride identified as a potential LPAR6 inhibitor.

Conclusions:

  • AGPAT3 plays a significant role in osteosarcoma prognosis and immune modulation.
  • Targeting LPA signaling and TAM activity, specifically through LPAR6, presents a promising therapeutic avenue for osteosarcoma, especially in combination with immunotherapy.
Keywords:
1-acylglycerol-3-phosphate O-acyltransferase 3lysophosphatidic acidosteosarcomasingle-celltumor-associated macrophages

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