Whole-genome microRNA expression profiling identifies a 5-microRNA signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme

Cancer. 2013 Feb 15;119(4):814-24. doi: 10.1002/cncr.27826. Epub 2012 Sep 18.

Abstract

Background: More reliable clinical outcome prediction is required to better guide more personalized treatment for patients with primary glioblastoma multiforme (GBM). The objective of this study was to identify a microRNA expression signature to improve outcome prediction for patients with primary GBM.

Methods: A cohort of Chinese patients with primary GBM (n = 82) was analyzed using whole-genome microRNA expression profiling with patients divided into a training set and a testing set. Cox regression and risk-score analyses were used to develop a 5-microRNA signature using 41 training samples. The signature was validated in 41 other test samples, in an independent cohort of 35 patients with GBM, and in the Cancer Genome Atlas data set.

Results: Patients who had high risk scores according to the 5-microRNA signature had poor overall survival and progression-free survival compared with patients who had low risk scores. Multivariate Cox analysis indicated that the 5-microRNA signature was an independent prognostic biomarker after adjusting for other clinicopathologic and genetic factors, such as extent of resection, temozolomide chemotherapy, preoperative Karnofsky performance status score, isocitrate dehydrogenase 1 (IDH1) mutation, and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status.

Conclusions: The 5-microRNA signature was identified as an independent risk predictor that identified patients who had a high risk of unfavorable outcome, demonstrating its potential for personalizing cancer management. The authors concluded that this signature should be evaluated in further prospective studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Asian People / genetics
  • Biomarkers, Tumor / genetics*
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / genetics*
  • Central Nervous System Neoplasms / mortality*
  • Cohort Studies
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / metabolism
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / therapeutic use
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics*
  • Glioblastoma / mortality*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Promoter Regions, Genetic
  • Reproducibility of Results
  • Temozolomide
  • Transcriptome
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • MicroRNAs
  • Tumor Suppressor Proteins
  • Dacarbazine
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide