Bulk and single-cell sequencing identified a prognostic model based on the macrophage and lipid metabolism related signatures for osteosarcoma patients

• Published in: Heliyon Vol. 10; no. 4; p. e26091
• Main Authors: Lin, Zili, Wu, Ziyi, Luo, Wei
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 29.02.2024; Elsevier
• Subjects: Chemoresistance; Immune infiltration; Lipid metabolism; Macrophage; Osteosarcoma; Lipid metabolism; Osteosarcoma; Chemoresistance; Immune infiltration; Macrophage
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e26091

The introduction of multidrug combination chemotherapy has significantly advanced the long-term survival prospects for osteosarcoma (OS) patients over the past decades. However, the escalating prevalence of chemoresistance has emerged as a substantial impediment to further advancements, necessitating the formulation of innovative strategies. Our present study leveraged sophisticated bulk and single-cell sequencing techniques to scrutinize the OS immune microenvironment, unveiling a potential association between the differentiation state of macrophages and the efficacy of OS chemotherapy. Notably, we observed that a heightened presence of lipid metabolism genes and pathways in predifferentiated macrophages, constituting the major cluster of OS patients exhibiting a less favorable response to chemotherapy. Subsequently, we developed a robust Macrophage and Lipid Metabolism (MLMR) risk model and a nomogram, both of which demonstrated commendable prognostic predictive performance. Furthermore, a comprehensive investigation into the underlying mechanisms of the risk model revealed intricate associations with variations in the immune response among OS patients. Finally, our meticulous drug sensitivity analysis identified a spectrum of potential therapeutic agents for OS, including AZD2014, Sapitinib, Buparlisib, Afuresertib, MIRA-1, and BIBR-1532. These findings significantly augment the therapeutic arsenal available to clinicians managing OS, presenting a promising avenue for elevating treatment outcomes.