Discovery of 5-Signature Predicting Survival of Patients with Lower-Grade Glioma.

OBJECTIVE: In the study, we aimed to identify key microRNAs (miRNAs) and clinical factors associated with survival time of lower-grade glioma (LGG) and develop an expression-based miRNA signature to provide survival risk prediction for patients with LGG. METHODS: We obtained miRNA expression profiles and clinical information of patients with LGG from The Cancer Genome Atlas dataset. All 591 miRNAs were modeled using random Forest Survival, Regression, and Classification to construct a random forest model for survival analysis, and feature selection was performed. We used univariate and multivariate Cox regression analysis to screen differentially expressed miRNAs and clinical factors related to overall survival of patients with LGG. RESULTS: A total of 591 differentially expressed miRNAs were obtained between LGG and normal tissues. After univariate and multivariate Cox regression analysis, 2 predictive miRNAs (hsa-miR-10b-5p and hsa-miR-15b-5p) and 3 clinical factors (grade, age, and cancer status) were finally screened out to construct a 5-signature, based on which patients in the training dataset were divided into high-risk and low-risk groups. The competitive performance of the 5-signature was revealed by receiver operating characteristic curve analysis. The prognostic value of the 5-signature was successfully validated in the testing and validation dataset. CONCLUSIONS: Our study demonstrated the promising potential of the novel 5-signature as an independent biomarker for survival prediction of patients with LGG.

Systemic analysis of genome-wide expression profiles identified potential therapeutic targets of demethylation drugs for glioblastoma.

Glioblastoma represents one of the most aggressive malignant brain tumors with high morbidity and motility. Demethylation drugs have been developed for its treatment with little efficacy has been observed. The purpose of this study was to screen therapeutic targets of demethylation drugs or bioactive molecules for glioblastoma through systemic bioinformatics analysis. We firstly downloaded genome-wide expression profiles from the Gene Expression Omnibus (GEO) and conducted the primary analysis through R software, mainly including preprocessing of raw microarray data, transformation between probe ID and gene symbol and identification of differential expression genes (DEGs). Secondly, functional enrichment analysis was conducted via the Database for Annotation, Visualization and Integrated Discovery (DAVID) to explore biological processes involved in the development of glioblastoma. Thirdly, we constructed protein-protein interaction (PPI) network of interested genes and conducted cross analysis for multi datasets to obtain potential therapeutic targets for glioblastoma. Finally, we further confirmed the therapeutic targets through real-time RT-PCR. As a result, biological processes that related to cancer development, amino metabolism, immune response and etc. were found to be significantly enriched in genes that differential expression in glioblastoma and regulated by 5'aza-dC. Besides, network and cross analysis identified ACAT2, UFC1 and CYB5R1 as novel therapeutic targets of demethylation drugs which also confirmed by real time RT-PCR. In conclusions, our study identified several biological processes and genes that involved in the development of glioblastoma and regulated by 5'aza-dC, which would be helpful for the treatment of glioblastoma.