Abstract
Glioma is characterized by rapid cell proliferation and extensive infiltration among brain tissues, but the molecular pathology has been still poorly understood. Previous studies found that DNA methylation modifications play a key role in contributing to the pathogenesis of glioma. On the other hand, long noncoding RNAs (lncRNAs) has been discovered to be associated with some key tumorigenic processes of glioma. Moreover, genomic methylation can influence expression and functions of lncRNAs, which contributes to the pathogenesis of many complex diseases. However, to date, no systematic study has been performed to detect the methylation of lncRNAs and its influences in glioma on a genome-wide scale. Here, we selected the methylation data, clinical information, expression of lncRNAs, and DNA methylation regulatory proteins of 537 glioma patients from TCGA and TANRIC databases. Then, we performed a differential analysis of lncRNA expression and methylated regions between low-grade glioma (LGG) and glioblastoma multiform (GBM) subjects, respectively. Next, we further identified and verified potential key lncRNAs contributing the pathogenesis of glioma involved in methylation modifications by an annotation and correlation analysis, respectively. In total, 18 such lncRNAs were identified, and 7 of them have been demonstrated to be functionally linked to the pathogenesis of glioma by previous studies. Finally, by the univariate Cox regression, LASSO regression, clinical correlation, and survival analysis, we found that all these 18 lncRNAs are high-risk factors for clinical prognosis of glioma. In summary, this study provided a strategy to explore the influence of lncRNA methylation on glioma, and our findings will be benefit to improve understanding of its pathogenesis.
Highlights
Glioma is the most common and highly malignant tumor in the intraparenchymal central nervous system (CNS) tumors [1]
We found a total of 537 glioma samples with the DNA methylation values, expression levels of protein-coding genes, and clinical information
For the 16 long noncoding RNAs (lncRNAs) highly expressed in glioblastoma multiform (GBM) patients, we found that the overall survival curve of the subjects with high lncRNA expression is significantly longer than the subjects with low lncRNA expression (p = 1.38 × 10−10) (Figure 3A)
Summary
Glioma is the most common and highly malignant tumor in the intraparenchymal central nervous system (CNS) tumors [1]. It is characterized by the rapid and extensive proliferation among brain tissues [2, 3]. Tremendous evidences shows that the DNA methylation is involved in tumorigenesis and development of the GBM [1, 7]. The promoter DNA methylation pattern of genes involved in RB1 and TP53 signaling pathways were identified in GBM patients [7]. The promoter methylation of the DNA repair enzyme (O6methylguanine-DNA methyltransferase) was discovered as a significant prognostic factor for temozolomide resistance in GBM patients [8]
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