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Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019
Identification of Candidate Genes Associated With Prognosis in Glioblastoma
Rongjie Li1, Qiulan Jiang2, Chunhai Tang3
1Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
Background:
Glioblastoma (GBM) is the most common malignant primary brain tumor, which associated with extremely poor prognosis.
Methods:
Data from datasets GSE16011, GSE7696, GSE50161, GSE90598 and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) between patients and controls. DEGs common to all five datasets were analyzed for functional enrichment and for association with overall survival using Cox regression. Candidate genes were further screened using least absolute shrinkage and selection operator (LASSO) and random forest algorithms, and the effects of candidate genes on prognosis were explored using a Gaussian mixed model, a risk model, and concordance cluster analysis. We also characterized the GBM landscape of immune cell infiltration, methylation, and somatic mutations.
Results:
We identified 3,139 common DEGs, which were associated mainly with PI3K-Akt signaling, focal adhesion, and Hippo signaling. Cox regression identified 106 common DEGs that were significantly associated with overall survival. LASSO and random forest algorithms identified six candidate genes (AEBP1, ANXA2R, MAP1LC3A, TMEM60, PRRG3 and RPS4X) that predicted overall survival and GBM recurrence. AEBP1 showed the best prognostic performance. We found that GBM tissues were heavily infiltrated by T helper cells and macrophages, which correlated with higher AEBP1 expression. Stratifying patients based on the six candidate genes led to two groups with significantly different overall survival. Somatic mutations in AEBP1 and modified methylation of MAP1LC3A were associated with GBM.
Conclusion:
We have identified candidate genes, particularly AEBP1, strongly associated with GBM prognosis, which may help in efforts to understand and treat the disease.
