Pathway changes in osteosarcoma pathogenesis under different metastatic states were clarified using gene set enrichment analysis (GSEA) of differentially expressed genes.<h4>Results</h4>A gene signature composed of 2 key prognosis-related genes (KCNJ5 and PFKFB2) was identified. The gene discussed is KCNJ5; the disease is osteosarcoma.