Up-regulation of microRNA-15b correlates with unfavorable prognosis and malignant progression of human glioma

Int J Clin Exp Pathol. 2015 May 1;8(5):4943-52. eCollection 2015.

Abstract

Recent studies have demonstrated that microRNA-15b (miR-15b) regulates cell cycle progression, proliferationnd apoptosis in glioma cells by targeting Cyclins. However, the clinical significance of miR-15b in human glioma remains unclear. Therefore, the aim of this study was to investigate the significance of miR-15b expression in diagnosis, prognosis and malignant progression of glioma. Quantitative real-time reverse transcriptive-PCR (qRT-PCR) was performed to examine miR-15b expression levels in 76 glioma tissues (13 grade II, 13 grade III and 50 grade IV gliomas) and seven glioma cell lines, as well as 10 non-neoplastic brain tissues and human astrocyte as control. MiR-15b showed significant increased expression in high-grade gliomas (P≤0.001) and glioma cells (fold change 2.8-7.6) relative to non-neoplastic brains and astrocyte, respectively. Additionally, high miR-15b expression was significantly associated with advanced WHO grade (P≤0.001), advanced patient age (P≤0.001) and low Karnofsky performance score (KPS, P≤0.001). Furthermore, Kaplan-Meier survival analysis and Cox regression analysis showed that patients with high miR-15b expression had significantly poor overall survival rate (P≤0.001) and miR-15b expression was an independent prognosis-predicting factor for glioma patients (P≤0.001; risk ratio=5.6), respectively. Moreover, miR-15b expression was examined in seven independent patients with primary grade II or III gliomas that spontaneously progressed to grade III or IV gliomas. Statistically significant higher expression (P=0.01) in the recurrent tumor compared with the corresponding primary tumor was observed in all of the seven patients. Our results suggest that miR-15b may be a prognostic predictor and be involved in malignant progression of glioma.

Keywords: glioma; malignant progression; miRNA-15b; microRNA; prognosis; up-regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Case-Control Studies
  • Cell Line
  • Chi-Square Distribution
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / mortality
  • Glioma / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Karnofsky Performance Status
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Proportional Hazards Models
  • Risk Factors
  • Up-Regulation

Substances

  • MIRN15 microRNA, human
  • MicroRNAs