Exploring the association mechanism between metastatic osteosarcoma and non-metastatic osteosarcoma based on dysfunctionality module.

PURPOSE Osteosarcoma (OS) is the primary malignant tumor which is common in children and adolescents. The treatment effect is still poor, though the treatment strategy has been dramatically improved. METHODS Differentially expressed genes in metastatic osteosarcoma and non-metastatic osteosarcoma were obtained first. Secondly, co-expression analysis has been processed for differentially expressed genes, and it is necessary to figure the gene drive of each module. Furthermore, both GO function and KEGG pathway enrichment analysis were performed on the module genes. Comprehensively, the module gene set which was predicted according to hypergeometric testing was importantly regulated by both transcription factors (TFs) and non-coding RNAs (ncRNAs). RESULTS Conclusively, 16 co-expression modules were obtained. ACAT1 and ATBF1 would actively regulate in dysfunction modules, and thus they are identified as osteosarcoma-driven genes. Enrichment results showed that the module genes were significantly involved in transcription factor activity, specific DNA binding of the RNA polymerase II proximal promoter sequence, DNA-binding transcriptional activator activity, ubiquitin-like protein transferase activity, and another biological process. Moreover, module genes significantly regulates FcγR-mediated phagocytosis, MAPK signaling pathway, phagocytosis, PI3K-Akt signaling pathway and others. Finally, we identified pivot ncRNAs (including CRNDE, miR-106a-5p, miR-181a-5p, etc) and pivot TFs (including NFKB1, STAT6, PPARG, RELA, etc) that significantly regulate dysfunction modules. CONCLUSION Overall, this work deciphered a co-expression network of common core pathogenic genes including metastatic osteosarcoma and non-metastatic osteosarcoma. It helps to identify core dysfunction modules and potential regulatory factors of the disease and improves understanding the underlying molecular association mechanisms between the two diseases.