From Single-cell Insights to Clinical Relevance: An M2 Macrophagebased Prognostic Model for Osteosarcoma

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• M2 macrophages contribute to an immunosuppressive tumor microenvironment (TME) in osteosarcoma (OS).
• The clinical significance of M2 macrophages in OS and their impact on treatment outcomes require further investigation.
• This study aimed to elucidate the role of M2 macrophages in OS and develop a predictive model.

Purpose of the Study:

• To develop a prognostic model for osteosarcoma (OS) based on M2 macrophage-associated genes.
• To evaluate the model's association with patient survival, immune infiltration, and drug sensitivity.
• To provide insights into risk stratification and therapeutic strategies for OS.

Main Methods:

• Utilized bulk and single-cell RNA sequencing data (TARGET-OS, GSE21257, GSE162454).
• Employed WGCNA and LASSO Cox regression to identify four key M2 macrophage-associated genes for a prognostic model.
• Assessed immune infiltration using ssGSEA, ESTIMATE, and MCP-counter; predicted drug sensitivity with oncoPredict.

Main Results:

• A four-gene risk model (LPAR5, MS4A4A, TNFSF8, VSIG4) was developed, correlating with OS patient survival.
• High-risk patients exhibited poorer survival and reduced immune cell infiltration (T cells, B cells, DCs, macrophages).
• The risk score demonstrated correlations with predicted drug sensitivity, suggesting a link to therapeutic response.

Conclusions:

• An M2 macrophage-related four-gene prognostic model for OS was successfully developed.
• The model is associated with survival outcomes, TME characteristics, and predicted drug sensitivity.
• These findings offer a basis for improved risk stratification and personalized treatment in osteosarcoma.