Identification of tumorigenicity-associated genes in osteosarcoma cell lines based on bioinformatic analysis and experimental validation

Osteosarcoma is the most common primary malignant tumor of bone. Tumorigenic investigation of osteosarcoma cell lines may facilitate preclinical studies of targeted therapy. Therefore, the aim of this study was to explore the tumorigenicity-associated genes in osteosarcoma cells. We found that 138 genes were highly expressed and 86 genes were lowly expressed in highly tumorigenic osteosarcoma cell lines (143B, MNNG/HOS, and SJSA-1) compared with poorly tumorigenic osteosarcoma cell lines (MG-63, Saos-2, and U-2 OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that highly expressed genes were associated with amino acids and energy metabolism, while lowly expressed genes were associated with cell cycle and DNA replication. Gene Ontology (GO) analysis showed that highly expressed genes were associated with endoplasmic reticulum stress response and aggrephagy, whereas lowly expressed genes were correlated with extracellular matrix assembly and DNA damage response. Further analysis identified six highly expressed genes and six lowly expressed genes. Three of highly expressed genes (DDX10, FOXA2, and HEY1) were correlated with poor prognosis, while three of lowly expressed genes (CYP26B1, GP1BB, and IFI44) showed the opposite trend in patients with osteosarcoma. Knockdown of HEY1 significantly inhibited the tumorigenicity of 143B cells in BALB/c nude mice.