Abstract
PURPOSE: To explore the exact molecular mechanisms underline osteosarcoma (OS) patients with lung metastases. METHODS: The differentially expressed gene (DEG) as well as differentially expressed miRNAs (DEMs) for OS lung metastases were deeply investigated with two independent sources of databases (GEO dataset and clinical participants); The enriched biological processes and signaling pathways were explored; the miRNAs-mRNAs network was constructed; the functions of potential DEGs and DEMs were also verified with external analysis. RESULTS: The OS patients with lung metastases displayed 323 DEGs as C-C motif chemokine ligand 3 (CCL3), sorting nexin 10 (SNX10), alpha-2-macroglobulin (A2M), carboxypeptidase E (CPE), Rap guanine nucleotide exchange factor 4 (RAPGEF4), PDZ domain containing 2 (PDZD2), calpain 10 (CAPN10), four and a half LIM domains 2 (FHL2), alkaline phosphatase, biomineralization associated (ALPL), interleukin 6 (IL6), solute carrier family 26 member 1 (SLC26A1) as well as smoothened, frizzled class receptor (SMO) were significant differentially expressed. At the same time, 21 DEMs were potential for the progress of OS lung metastasis with hsa-miR-638, hsa-miR-451, hsa-miR-486-5p, hsa-miR-134 and hsa-miR-648 were significant distinct. It could been shown that hsa-miR-638 manipulated the largest number of target genes. The functions of hsa-miR-638 and target mRNAs for the development of lung metastasis in OS could be confirmed by quantitative Real-time PCR analysis. CONCLUSION: This integrated study hypothesized several miRNA dependent signaling pathway for OS patients with lung metastases and initiated a potential strategy for better understanding the lung metastases in clinic.