RESUMEN
Background: This study sought to identify potential key genes for osteosarcoma metastasis and analyze their immune infiltration patterns using bioinformatic methods. Methods: We obtained transcriptomic data related to osteosarcoma and osteosarcoma with metastasis from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) and The Gene Expression Omnibus (GEO) databases and identified the differentially expressed genes (DEGs). We also identified potential key genes for osteosarcoma metastasis by a protein-protein interaction network analysis, and we conducted a Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify the core genes for prognosis, immune cell infiltration, and drug sensitivity, and the risk prediction and prognosis models of metastasis were constructed. Results: By comparing the transcriptome data of osteosarcomas without metastasis and those with metastasis, a total of 19 core DEGs were identified, and the GO and KEGG analyses revealed an association between these DEGs and the regulation of cell division, secretory granule lumen, the Ras-associated protein 1 (Rap1) signaling pathway, and the mitogen-activated protein kinase (MAPK) signaling pathway. Compared with other immune cells, macrophage infiltration was predominant in osteosarcoma samples with metastatic osteosarcoma, and insulin-like growth factors-1 (IGF1) and myelocytomatosis protein 2 (MYC2) genes were predicted to more than 50 targeted therapeutic agents. A metastasis prediction model with 5 genes [i.e., ecotropic viral integration site 2B (EVI2B), CCAAT/enhancer binding protein (CEBPA), lymphocyte cytosolic protein 2 (LCP2), selectin L (SELL), and Niemann-Pick disease, type C2A (NPC2A)], and a prognostic model with 4 genes [i.e., insulin-like growth factors-2 (IGF2), cathepsin O (CTSO), Niemann-Pick disease, type C2 (NPC2), and amyloid beta (A4) precursor protein-binding, family B, member 1 interacting protein (APBB1IP)] were developed. Conclusions: We constructed a metastasis prediction model with 5 genes (i.e., EVI2B, CEBPA, LCP2, SELL, and NPC2A), and a prognostic model with 4 genes (i.e., IGF2, CTSO, NPC2, and APBB1IP) that may be potential biomarkers for osteosarcoma metastasis. Macrophages are the predominant immune infiltrating cells in osteosarcoma metastasis and may provide a new direction for the treatment of osteosarcoma.
