Genome-wide methylation profiling reveals new biomarkers for prognosis prediction of glioblastoma.
OBJECTIVE
To identify a specific hypermethylated molecular biomarker for human malignant glioblastoma prognosis.


METHODS
Genome-wide methylation profiling was performed on 33 tumors and 3 normal glioblastoma samples using the Infinium HumanMethylation450 microarray. Cluster analysis was carried out in these samples according to the differentiated methylated genes. DNA methylation of selected significant candidates was subsequently validated to analyze the association of methylation status of these genes with overall survival as well as gene expression.


RESULTS
We found 217 hypermethylated CpG sites located in 210 respective genes with significant differences in short- and long-term survival (STS and LTS) samples (P < 0.01). Cluster analysis revealed fine clustering of genes with LTS and STS. Of these, we selected 10 most hypermethylated genes, including IL11, RRAD, MS4A6A, SNAPC2, ALDH1A3, ADCY1, MMS19L, NDUFB8, POMC, and THSD4, to perform cluster analysis. It came out with the same fine classification and with survival time of these patients. The top ranking genes were further examined to compare their methylation status with the overall survival rate of patients, as well as with gene expression levels.


CONCLUSIONS
We obtained a featured global profiling of DNA methylation in glioblastoma. Our findings strongly indicate that epigenetic silencing of IL11, RRAD, MS4A6A, SNAPC2, and ALDH1A3 are common events in glioblastoma which could be used as novel biomarkers for the prognosis of glioblastoma.
Jiangong
J
Ma
Xin
X
Hou
Mingxuan
M
Li
Hongyu
H
Ren
Shumin
S
Fang
Xiaobin
X
Wang
Department of Neurosurgery, The First Affiliated Hospital of Henan University, Kaifeng 475000, Henan Province, PR, China.
Cheng
C
He
D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study / Q000379:methods; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D008297:Male; D011379:Prognosis; D015203:Reproducibility of Results