HDAC3 Expression Correlates with the Prognosis and Grade of Patients with Glioma: A Diversification Analysis Based on Transcriptome and Clinical Evidence

World Neurosurg. 2018 Nov:119:e145-e158. doi: 10.1016/j.wneu.2018.07.076. Epub 2018 Jul 24.

Abstract

Objective: This study aimed to clarify the relationship between histone deacetylase 3 (HDAC3) expression and the prognosis as well as the grade of patients with glioma.

Methods: The quantitative real-time polymerase chain reaction was profiled to examine the HDAC3 expression in glioma and normal glial cell lines. An Oncomine database analysis and prognosis analysis were performed. The correlation between World Health Organization (WHO) grade and HDAC3 was analyzed by Spearman rank correlation test. A meta-analysis was performed to confirm the conclusion.

Results: HDAC3 RNA overexpression in glioma cell lines was detected (P < 0.05). Four data sets were screened from the Oncomine database and showed that the expression level of HDAC3 was consistently higher in glioma than in normal tissue (P < 0.001). The prognostic analysis of 325 glioma samples from the Chinese Glioma Genome Atlas showed that patients with low HDAC3 expression had significantly better overall survival (OS) and progression-free survival (PFS) than did patients with high HDAC3 expression [hazard ratio [HR], 1.992; 95% confidence interval [CI], 1.490-2.662; P < 0.0001 and HR, 1.874; 95% CI, 1.412-2.487; P < 0.0001, respectively]. Both the WHO grade III group and the WHO grade IV group expressed significantly higher messenger RNA (mRNA) level than did the WHO grade II group (P < 0.05). Four cohort studies consisting of 490 patients were included in the meta-analysis. The pooled data of subgroup analysis showed significantly longer OS in low HDAC3 mRNA level [HR, 3.38; 95% CI, 1.80-6.37; P = 0.0002].

Conclusions: HDAC3 mRNA was expressed more in glioma than in the normal glial cell line. Low HDAC3 mRNA expression levels predicted better OS. HDAC3 expression could be a biomarker to discriminate glioma grade.

Keywords: CGGA; Chinese Glioma Genome Atlas; Glioma; HDAC3; Overall survival; Prognosis; WHO grade.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioma / diagnosis*
  • Glioma / metabolism*
  • Glioma / mortality
  • Glioma / therapy
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Prognosis
  • RNA, Messenger / metabolism
  • Survival Analysis
  • Transcriptome*

Substances

  • RNA, Messenger
  • Histone Deacetylases
  • histone deacetylase 3