SIRT5 downregulation is associated with poor prognosis in glioblastoma

Cancer Biomark. 2019;24(4):449-459. doi: 10.3233/CBM-182197.

Abstract

Objective: Sirtuins (SIRT) are NAD+-dependent protein deacetylases that are involved in the regulation of cancer-associated pathways. However, the biological role of these deacetylases remains elusive in glioblastoma (GBM). Here, we evaluated the effects of 7 sirtuins regarding their occurrence and prognostic value for GBM.

Methods: In this research, the effects of SIRT5 on the occurrence and prognosis of GBM were evaluated using integrative bioinformatics analyses.

Results: Based on comprehensive analyses of data obtained from web-based bioinformatics platforms, the data demonstrate that only SIRT5 expression is statistically decreased in GBM tissues. The clinical relevance analysis shows that downregulation of SIRT5 is significantly correlated with a shorter survival time. Moreover, the expression levels of SIRT5 were confirmed to be negatively associated with DNA methylation status. In addition, a protein-protein interaction network was constructed to determine the relationship of genes coexpressed with SIRT5. Functional enrichment analysis revealed that SIRT5 was potentially involved in epithelial-mesenchymal transition and in regulating cell communications.

Conclusions: Collectively, our results indicate that SIRT5 acts as a potential suppresser during tumorigenesis, and suggest that SIRT5 may be a promising prognostic biomarker of GBM.

Keywords: DNA methylation; Glioblastoma; SIRT5; overall survival; prognosis.

MeSH terms

  • Biomarkers, Tumor*
  • Computational Biology / methods
  • CpG Islands
  • DNA Methylation
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genomics / methods
  • Glioblastoma / genetics*
  • Glioblastoma / mortality*
  • Glioblastoma / pathology
  • Humans
  • Prognosis
  • Sirtuins / genetics*

Substances

  • Biomarkers, Tumor
  • SIRT5 protein, human
  • Sirtuins