Investigating age‑induced differentially expressed genes and potential molecular mechanisms in osteosarcoma based on integrated bioinformatics analysis

Mol Med Rep. 2019 Apr;19(4):2729-2739. doi: 10.3892/mmr.2019.9912. Epub 2019 Jan 30.

Abstract

Osteosarcoma (OS) is the most common primary bone malignancy. It predominantly occurs in adolescents, but can develop at any age. The age at diagnosis is a prognostic factor of OS, but the molecular basis of this remains unknown. The current study aimed to identify age‑induced differentially expressed genes (DEGs) and potential molecular mechanisms that contribute to the different outcomes of patients with OS. Microarray data (GSE39058 and GSE39040) obtained from the Gene Expression Omnibus database and used to analyze age‑induced DEGs to reveal molecular mechanism of OS among different age groups (<20 and >20 years old). Differentially expressed mRNAs (DEMs) were divided into up and downregulated DEMs (according to the expression fold change), then Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed. Furthermore, the interactions among proteins encoded by DEMs were integrated with prediction for microRNA‑mRNA interactions to construct a regulatory network. The key subnetwork was extracted and Kaplan‑Meier survival analysis for a key microRNA was performed. DEMs within the subnetwork were predominantly involved in 'ubiquitin protein ligase binding', 'response to growth factor', 'regulation of type I interferon production', 'response to decreased oxygen levels', 'voltage‑gated potassium channel complex', 'synapse part', 'regulation of stem cell proliferation'. In summary, integrated bioinformatics was applied to analyze the potential molecular mechanisms leading to different outcomes of patients with OS among different age groups. The hub genes within the key subnetwork may have crucial roles in the different outcomes associated with age and require further analysis.

MeSH terms

  • Biomarkers, Tumor
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / mortality
  • Computational Biology* / methods
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Humans
  • Kaplan-Meier Estimate
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism*
  • Osteosarcoma / mortality
  • Prognosis
  • Protein Interaction Mapping
  • Protein Interaction Maps

Substances

  • Biomarkers, Tumor