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Abstract Objectives Osteosarcoma stands as a highly aggressive primary bone malignancy with a notable penchant for metastasis and a grim prognosis. The exploration of metabolic gene signatures, particularly those involved in glycolysis and cholesterol synthesis, has recently garnered attention for their potential to predict cancer progression and therapeutic outcomes. This study probes the prognostic value of a glycolysis and cholesterol synthesis-related gene signature (GCSRG) in osteosarcoma, along with its influence on the tumor immune microenvironment. Methods A comprehensive bioinformatics approach was applied to osteosarcoma samples from the TCGA database, incorporating unsupervised clustering to delineate patient subsets, differential gene expression analysis to identify key metabolic pathways, and survival analysis to ascertain prognostic validity. Results The investigation yielded a distinct GCSRG with significant prognostic capabilities. Notably, a high GCSRG score correlated with worse patient outcomes but revealed a marked enrichment in immune cell infiltration within the tumor milieu, suggesting a complex relationship between metabolism and immune surveillance in osteosarcoma. Conclusion The GCSRG emerges as a promising biomarker for osteosarcoma prognosis, offering new vistas for assessing patient suitability for immunotherapeutic interventions. The potential of the GCSRG to act as a guide for personalized treatment strategies is highlighted, underscoring the need for strategic therapeutic modulation based on metabolic and immune interactions to improve patient prognosis in osteosarcoma.
Feng et al. (Fri,) studied this question.