MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients

Cancer Sci. 2011 Dec;102(12):2186-90. doi: 10.1111/j.1349-7006.2011.02092.x. Epub 2011 Oct 12.


Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM. In a group of 38 patients with primary GBM, we analyzed the expression of eight microRNAs (miR-21, miR-128a, miR-181c, miR-195, miR-196a, miR-196b, miR-221, and miR-222). In addition, we examined the methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter by high-resolution melting analysis, as this has been shown to be a predictive marker in GBM. MGMT methylation status correlated with progression-free survival (P = 0.0201; log-rank test) as well as with overall survival (P = 0.0054; log-rank test). MiR-195 (P = 0.0124; log-rank test) and miR-196b (P = 0.0492; log-rank test) positively correlated with overall survival. Evaluation of miR-181c in combination with miR-21 predicted time to progression within 6 months of diagnosis with 92% sensitivity and 81% specificity (P < 0.0001). Our data confirmed that the methylation status of MGMT but also miR-21, miR-181c, miR-195, and miR-196b to be associated with survival of GBM patients. Above all, we suggest that the combination of miR-181c and miR-21 could be a very sensitive and specific test to identify patients at high risk of early progression after surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality
  • DNA Methylation
  • DNA Modification Methylases / genetics*
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics*
  • DNA Repair Enzymes / metabolism
  • Disease-Free Survival
  • Female
  • Glioblastoma / diagnosis*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / mortality
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic*
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism


  • Biomarkers, Tumor
  • MIRN195 microRNA, human
  • MIRN196 microRNA, human
  • MIRN21 microRNA, human
  • MIrn181 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes