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Exploring the relationship between metabolism and immune microenvironment in osteosarcoma based on metabolic pathways
Changwu Wu1,2, Jun Tan3,4, Hong Shen5,6,7
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Journal of Biomedical Science
|January 11, 2024
Summary
Metabolic pathways, particularly vitamin and cofactor metabolism, significantly impact osteosarcoma
Area of Science:
- * Oncology
- * Molecular Biology
- * Immunology
Background:
- * Metabolic reprogramming is crucial in osteosarcoma, influencing prognosis and treatment outcomes.
- * The interplay between tumor metabolism and the tumor immune microenvironment (TIME) in osteosarcoma requires further elucidation.
Purpose of the Study:
- * To investigate the relationship between metabolic pathways and the TIME in osteosarcoma.
- * To identify metabolic features that predict treatment response and patient prognosis.
- * To explore the functional role of key metabolism-related genes in osteosarcoma progression.
Main Methods:
- * Analysis of RNA-Seq and clinical data from TARGET and GEO databases (n=84).
- * Inference of metabolic super-pathway activity and immune cell infiltration.
- * Unsupervised clustering to identify metabolic and metabolism-related gene (MRG) clusters.
- * Construction and validation of an MRG-based risk model.
- * Molecular experiments to assess the function of ST3GAL4 in osteosarcoma cells.
Main Results:
- * Vitamin and cofactor metabolism strongly correlates with osteosarcoma prognosis and TIME.
- * Two distinct metabolic clusters (C1, C2) showed differential immune infiltration and chemotherapeutic response (C2 superior).
- * Three MRG clusters (GC1-3) exhibited distinct prognoses and immune infiltration levels; GC3 predicted better response to immunotherapy and chemotherapy.
- * A validated metabolism-related risk model demonstrated prognostic predictive power, with low-risk groups showing higher immune infiltration.
- * ST3GAL4 knockdown suppressed osteosarcoma cell proliferation, invasion, glycolysis, and M2 macrophage polarization.
Conclusions:
- * Vitamin and cofactor metabolism are key regulators of osteosarcoma TIME and prognosis.
- * MRG clusters effectively reflect TIME alterations and predict responses to chemotherapy and immunotherapy.
- * The developed metabolism-related risk model shows promise for prognostic prediction in osteosarcoma.
- * ST3GAL4 is implicated in osteosarcoma progression, glycolysis, and modulation of the TIME.
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