Dataset Information

Dysregulated Expression and Methylation Analysis Identified TLX1NB as a Novel Recurrence Marker in Low-Grade Gliomas.

ABSTRACT: Low-grade gliomas (LGGs) are the most common CNS tumors, and the main therapy for LGGs is complete surgical resection, due to its curative effect. However, LGG recurrence occurs frequently. Biomarkers play a crucial role in evaluating the recurrence and prognosis of LGGs. Numerous studies have focused on LGG prognosis. However, the multiomics research investigating the roles played by gene methylation and expression in LGG recurrence remains limited. In this study, we integrated the TCGA and GEO datasets, analyzing RNA and methylation data for recurrence (R) and nonrecurrence (NR) groups. We found a low expression of TLX1NB and high methylation in recurrence patients. Low expression of TLX1NB is associated with poor survival (OS: p = 0.04). The expression of TLX1NB is likely to play a role in the prognosis of LGG. Therefore, TLX1NB may represent an alternative early biomarker for the recurrence of low-grade gliomas.

SUBMITTER: Duan H

PROVIDER: S-EPMC7576335 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Dysregulated Expression and Methylation Analysis Identified <i>TLX1NB</i> as a Novel Recurrence Marker in Low-Grade Gliomas.

Duan Hongzhou H Yang Zuozhen Z Li Chen C Zhang Jiayong J Shen Shengli S Yuan Changwei C Wang Yingjin Y

International journal of genomics 20201012

Low-grade gliomas (LGGs) are the most common CNS tumors, and the main therapy for LGGs is complete surgical resection, due to its curative effect. However, LGG recurrence occurs frequently. Biomarkers play a crucial role in evaluating the recurrence and prognosis of LGGs. Numerous studies have focused on LGG prognosis. However, the multiomics research investigating the roles played by gene methylation and expression in LGG recurrence remains limited. In this study, we integrated the TCGA and GEO ...[more]

PMID: 33102572

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Project description:Despite a generally better prognosis than high-grade glioma (HGG), recurrence and malignant progression are the main causes for the poor prognosis and difficulties in the treatment of low-grade glioma (LGG). It is of great importance to learn about the risk factors and underlying mechanisms of LGG recurrence and progression. In this study, the transcriptome characteristics of four groups, namely, normal brain tissue and recurrent LGG (rLGG), normal brain tissue and secondary glioblastoma (sGBM), primary LGG (pLGG) and rLGG, and pLGG and sGBM, were compared using Chinese Glioma Genome Atlas (CGGA) and Genotype-Tissue Expression Project (GTEx) databases. In this study, 296 downregulated and 396 upregulated differentially expressed genes (DEGs) with high consensus were screened out. Univariate Cox regression analysis of data from The Cancer Genome Atlas (TCGA) yielded 86 prognostically relevant DEGs; a prognostic prediction model based on five key genes (HOXA1, KIF18A, FAM133A, HGF, and MN1) was established using the least absolute shrinkage and selection operator (LASSO) regression dimensionality reduction and multivariate Cox regression analysis. LGG was divided into high- and low-risk groups using this prediction model. Gene Set Enrichment Analysis (GSEA) revealed that signaling pathway differences in the high- and low-risk groups were mainly seen in tumor immune regulation and DNA damage-related cell cycle checkpoints. Furthermore, the infiltration of immune cells in the high- and low-risk groups was analyzed, which indicated a stronger infiltration of immune cells in the high-risk group than that in the low-risk group, suggesting that an immune microenvironment more conducive to tumor growth emerged due to the interaction between tumor and immune cells. The tumor mutational burden and tumor methylation burden in the high- and low-risk groups were also analyzed, which indicated higher gene mutation burden and lower DNA methylation level in the high-risk group, suggesting that with the accumulation of genomic mutations and epigenetic changes, tumor cells continued to evolve and led to the progression of LGG to HGG. Finally, the value of potential therapeutic targets for the five key genes was analyzed, and findings demonstrated that KIF18A was the gene most likely to be a potential therapeutic target. In conclusion, the prediction model based on these five key genes can better identify the high- and low-risk groups of LGG and lay a solid foundation for evaluating the risk of LGG recurrence and malignant progression.

Dataset Information

Dysregulated Expression and Methylation Analysis Identified TLX1NB as a Novel Recurrence Marker in Low-Grade Gliomas.

Publications

Dysregulated Expression and Methylation Analysis Identified <i>TLX1NB</i> as a Novel Recurrence Marker in Low-Grade Gliomas.

Similar Datasets

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