Osteosarcoma is the most common type of primary malignant bone tumor observed in children and adolescents. The aim of the present study was to identify an osteosarcoma-related gene module (OSM) by looking for a dense module following the integration of signals from genome-wide association studies (GWAS) into the human protein-protein interaction (PPI) network. A dataset of somatic mutations in osteosarcoma was obtained from the dbGaP database and their testing P-values were incorporated into the PPI network from a recent study using the dmGWAS bioconductor package. An OSM containing 201 genes (OS genes) and 268 interactions, which were closely associated with immune response, intracellular signal transduction and cell activity was identified. Topological analysis of the OSM identified 11 genes, including APP, APPBP2, ATXN1, HSP90B1, IKZF1, KRTAP10-1, PAK1, PDPK1, SMAD4, SUZ12 and TP53 as potential diagnostic biomarkers for osteosarcoma. The overall survival analysis of osteosarcoma for those 11 genes based on a dataset from the Cancer Genome Atlas, identified APP, HSP90B1, SUZ12 and IKZF1 as osteosarcoma survival-related genes. The results of the present study should be helpful in understanding the diagnosis and treatment of osteosarcoma and its underlying mechanisms. In addition, the methodology used in the present study may be suitable for the analysis of other types of disease.
Keywords: dbGaP; disease module; network; osteosarcoma; protein-protein interaction.