Correlation of MicroRNA 132 Up-regulation with an Unfavorable Clinical Outcome in Patients with Primary Glioblastoma Multiforme Treated with Radiotherapy Plus Concomitant and Adjuvant Temozolomide Chemotherapy.
BACKGROUND
MicroRNA 132 (miR-132) is dysregulated in a range of human malignancies; however, its role in glioma has not been reported. The aim of this study was to profile miR-132 expression in a cohort of patients with primary glioblastoma multiforme (GBM) treated with the Stupp regimen and to correlate microRNA levels with patient outcome.


METHODS
miR-132 levels relative to RNU44 were assessed by quantitative reverse transcription-polymerase chain reaction in 43 GBMs and normal brain tissue. The cohort comprised patients less than 72 years of age with Eastern Cooperative Oncology Group (ECOG) scores between 0 and 2 who had undergone 6-week concomitant radiation and temozolomide followed by adjuvant temozolomide. Survival data were available for all cases. Tumors were characterized for O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH) 1/2 mutation status. Associations between miR-132 expression and clinical indicators were analyzed.


RESULTS
Tumor miR-132 levels ranged from 0.07- to 40.4-fold increase (mean = 5.5-fold increase) relative to normal brain. High-level miR-132 (above the mean) independently predicted for a significantly shorter overall survival (P = .008). miR-132 was a stronger prognostic indicator than ECOG score (P = .012) and age at diagnosis (P = .026) but did not correlate with MGMT methylation status or extent of tumor resection. Cox regression analysis confirmed high miR-132 as the strongest predictor of outcome (P = .010) with a hazard ratio of 2.8.


CONCLUSIONS
This study identified high miR-132 expression as a biomarker of poor prognosis in patients with primary GBM treated with the Stupp regimen.
Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia ; University of Sydney, Sydney, New South Wales, Australia.
Nicole R
NR
Parker
University of Sydney, Sydney, New South Wales, Australia.
Nelson
N
Correia
University of Sydney, Sydney, New South Wales, Australia.
Brendan
B
Crossley
University of Sydney, Sydney, New South Wales, Australia ; Department of Neuropathology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia ; Brain and Mind Research Institute, Camperdown, New South Wales, Australia.
Michael E
ME
Buckland
Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia ; University of Sydney, Sydney, New South Wales, Australia.
Viive M
VM
Howell
Bill Walsh Translational Cancer Research Laboratory, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia ; University of Sydney, Sydney, New South Wales, Australia ; Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales, Australia ; Sydney Neuro-Oncology Group, North Shore Private Hospital, St Leonards, New South Wales, Australia.
Helen R
HR
Wheeler