Identification of critical genes and gene interaction networks that mediate osteosarcoma metastasis to the lungs.

Abstract

Osteosarcoma (OS) is the most commonly diagnosed bone tumor in young adults under the age of 20. Metastasis is considered an important factor underlying cancer-associated morbidity and mortality, and, as a result, the survival rate of patients with metastatic OS is low. In spite of this, the mechanisms underlying metastasis in OS are currently not well understood. The present study compared gene expression levels between five non-metastatic and four metastatic OS tumor samples, using an Affymetrix microarray. A total of 282 genes were differentially expressed in the metastatic samples, as compared with the non-metastatic samples. Of these differentially expressed genes (DEGs), 212 were upregulated and 70 were downregulated. The following DEGs were associated with metastasis: Homeobox only protein; lysosomal-associated membrane protein-3; chemokine (C-C motif) ligand-18; carcinoembryonic antigen-related cell adhesion molecule-6; keratin-19; prostaglandin-endoperoxide synthase-2; clusterin; and nucleoside diphosphate kinase-1. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were conducted, which identified 529 biological processes (P<0.01) and 10 KEGG pathways (P<0.05) that were significantly over-represented in the metastatic samples, as compared with the non-metastatic samples. Interaction networks for the DEGs were constructed using the corresponding GO terms and KEGG pathways, and these identified numerous genes that may contribute to OS metastasis. Among the enriched biological processes, four DEGs were consistently over-represented: Jun proto-oncogene, caveolin-1, nuclear factor-κB-inhibitor-α and integrin alpha-4; thus suggesting that they may have key roles in OS metastasis, and may be considered potential therapeutic targets in the treatment of patients with OS.