Background: Metastasis is the leading cause of death for patients with osteosarcoma (OS). In the present study, we explore the biomarkers for metastatic OS and provide potential therapeutic approaches.
Materials and Methods: RNA-Seq data and clinical follow-up information were downloaded from TARGET and GEO databases. A Cox regression model was used to analyze metastatic events. L1000FWD, DGIdb, and CMap databases were used to identify potential drugs related to metastasis. Invasion and migration transwell assays and an adhesion assay were used to identify biological functions of genes.
Results: A total of 15 metastasis-related signatures (MRSs) were associated with the prognosis based on the TARGET or GSE21257 cohorts, among which IL10RA  and TLR7  genes were especially significant. In the DGIdb drug–gene interaction database, TLR7  and IFNGR1  were found to have potential interactions with drugs. After inhibiting the expression of TLR7 , the migration, invasion, and adhesion ability of OS cells were significantly enhanced, which further promoted metastasis.
Conclusion: We identified a set of MRS that may be related to OS metastases. Among them, TLR7  plays a vital role and may be a potential target for OS metastasis treatment.
Keywords: osteosarcoma, metastatic-related signatures, drug–gene interaction, TLR7, migration, invasion