Upregulation of miR-125b, miR-181d, and miR-221 Predicts Poor Prognosis in MGMT Promoter-Unmethylated Glioblastoma Patients

Am J Clin Pathol. 2018 Mar 29;149(5):412-417. doi: 10.1093/ajcp/aqy008.

Abstract

Objectives: To evaluate the prognostic values of microRNAs (miRNAs) in glioblastoma, and to see if there is an association between miRNAs and MGMT promoter methylation status.

Methods: We collected paraffin blocks from resection specimens from 114 glioblastoma patients who had received temozolomide treatment and radiotherapy. Real-time quantitative PCR was performed to determine the expression levels of five miRNAs.

Results: Upregulation of miR 125b-5p, miR 181d-3p, miR 221-3p, miR-222-3p, and miR 224-5p was observed in 13.2%, 5.3%, 12.3%, 32.5%, and 78.9% of the cases, respectively. The expression level of miRNAs was not significantly different in tumors with MGMT promoter methylation vs tumors without such methylation. Upregulation of miR 125b-5p, miR 181d-3p, or miR 221-3p was significantly associated with shorter survival in MGMT-unmethylated glioblastoma patients.

Conclusions: miR 125b-5p, miR 181d-3p, and miR 221-3p are useful in predicting poor prognosis in patients with MGMT-unmethylated glioblastomas.

MeSH terms

  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • DNA Methylation
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Glioblastoma / diagnosis*
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Survival Analysis
  • Temozolomide / therapeutic use
  • Tumor Suppressor Proteins / genetics*
  • Up-Regulation

Substances

  • MIRN125 microRNA, human
  • MIRN221 microRNA, human
  • MIrn181 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide