Integrated analysis of genome-wide DNA methylation, gene expression and protein expression profiles in molecular subtypes of WHO II-IV gliomas.
BACKGROUND
Glioma is the most common malignant primary brain tumor among adults, among which glioblastoma (GBM) exhibits the highest malignancy. Despite current standard chemoradiation, glioma is still invariably fatal. A further insight into the molecular background of glioma is required to improve patient outcomes.


METHODS
Previous studies evaluated molecular genetic differences through comparing different grades of glioma. Here, we integrated DNA methylation, RNA sequencing and protein expression data sets of WHO grade II to IV gliomas, to screen for dysregulated genes in subtypes during malignant progression of glioma.


RESULTS
We propose a list of universal genes (UG) as novel glioma biomarkers: 977 up-regulated genes and 114 down-regulated genes, who involved in cell cycle, Wnt receptor signaling pathway and fatty acid metabolic process. Poorer survival was associated significantly with the high expression of 977 up-regulated genes and low expression of 114 down-regulated in UG (P <0.001).


CONCLUSIONS
To our knowledge, this was the first study that focused on subtypes to detect dysregulated genes that could contribute to malignant progression. Furthermore, the differentially expressed genes profile may lead to the identification of new therapeutic targets for glioma patients.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6 TiantanXili, Dongcheng District, Beijing, 100050, China. simon910@126.com.
Zhi-Liang
ZL
Wang
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. chuanbao123@139.com.
Chuan-Bao
CB
Zhang
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. caijinquan666777@126.com.
Jin-Quan
JQ
Cai
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. sixwin121@126.com.
Qing-Bin
QB
Li
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. wangzheng1024@126.com.
Zheng
Z
Wang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6 TiantanXili, Dongcheng District, Beijing, 100050, China. taojiang1964@163.com.|Beijing Neurosurgical Institute, Capital Medical University, Beijing, China. taojiang1964@163.com.|Beijing Institute for Brain Disorders Brain Tumor Center, Beijing, China. taojiang1964@163.com.|China National Clinical Research Center for Neurological Diseases, Beijing, China. taojiang1964@163.com.
Tao
T
Jiang
D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D058977:Molecular Sequence Annotation; D011379:Prognosis; D020543:Proteome; D040901:Proteomics; D015203:Reproducibility of Results; D059467:Transcriptome
D014408:Biomarkers, Tumor; D020543:Proteome