Identification of intrinsic subtype-specific prognostic microRNAs in primary glioblastoma.
BACKGROUND
Glioblastoma multiforme (GBM) is the most malignant type of glioma. Integrated classification based on mRNA expression microarrays and whole-genome methylation subdivides GBM into five subtypes: Classical, Mesenchymal, Neural, Proneural-CpG island methylator phenotype (G-CIMP) and Proneural-non G-CIMP. Biomarkers that can be used to predict prognosis in each subtype have not been systematically investigated.


METHODS
In the present study, we used Cox regression and risk-score analysis to construct respective prognostic microRNA (miRNA) signatures in the five intrinsic subtypes of primary glioblastoma in The Cancer Genome Atlas (TCGA) dataset.


RESULTS
Patients who had high-risk scores had poor overall survival compared with patients who had low-risk scores. The prognostic miRNA signature for the Mesenchymal subtype (four risky miRNAs: miR-373, miR-296, miR-191, miR-602; one protective miRNA: miR-223) was further validated in an independent cohort containing 41 samples.


CONCLUSIONS
We report novel diagnostic tools for deeper prognostic sub-stratification in GBM intrinsic subtypes based upon miRNA expression profiles and believe that such signature could lead to more individualized therapies to improve survival rates and provide a potential platform for future studies on gene treatment for GBM.
Rui
R
Li
Kaiming
K
Gao
Hui
H
Luo
Xiefeng
X
Wang
Yan
Y
Shi
Qingsheng
Q
Dong
WenKang
W
Luan
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, No,300, Guangzhou Road, Gulou District, Nanjing 210029, PR China. yypl9@njmu.edu.cn.
Yongping
Y
You
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D005909:Glioblastoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D025202:Molecular Diagnostic Techniques; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012306:Risk; D059467:Transcriptome
D014408:Biomarkers, Tumor; D035683:MicroRNAs