Dataset Information

Clinical and Biological Significances of a Methyltransferase-Related Signature in Diffuse Glioma.

ABSTRACT: Methylation of DNA, RNA or protein is a reversible modification. The proteins and genes that regulate this modification can be a candidate target for tumor therapy. However, the characteristics of methyltransferase related genes in glioma remain obscure. In this study, we systematically analyzed the relationship between methyltransferase-related genes expression profiles and outcomes in glioma patients based on The Cancer Genome Atlas and Chinese Glioma Genome Atlas RNA sequencing datasets. Consensus clustering identified two robust groups with significantly different pathological features and prognosis. Then a methyltransferase-related risk signature was built by a Cox proportional hazards model with elastic net penalty. Moreover, the risk score is associated with patients' clinical and molecular features and can be used as an independent prognostic indicator for patients with glioma. Furthermore, genes associated with the high-risk group were involved in various aspects of the malignant progression of glioma via Gene Ontology analysis and Gene Set Enrichment Analysis. In summary, our study identified a methyltransferase-related risk signature for predicting the prognosis of gliomas.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7185060 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Clinical and Biological Significances of a Methyltransferase-Related Signature in Diffuse Glioma.

Zhang Ying Y Liu Yuqing Y Liu Hanjie H Zhao Zheng Z Wu Fan F Zeng Fan F

Frontiers in oncology 20200420

Methylation of DNA, RNA or protein is a reversible modification. The proteins and genes that regulate this modification can be a candidate target for tumor therapy. However, the characteristics of methyltransferase related genes in glioma remain obscure. In this study, we systematically analyzed the relationship between methyltransferase-related genes expression profiles and outcomes in glioma patients based on The Cancer Genome Atlas and Chinese Glioma Genome Atlas RNA sequencing datasets. Cons ...[more]

PMID: 32373523

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Project description:BackgroundDiffuse glioma is the most common primary tumor of the central nervous system and has a poor prognosis. Recently, a new type of programmed cell death (PCD), pyroptosis, has been found to be widely involved in the process of tumor diseases. However, the expression of pyroptosis-related genes (PRGs) in diffuse gliomas and their relationship with prognosis have rarely been evaluated.MethodsIn this study, we obtained RNA sequencing and clinical data from the Cancer Genome Atlas (TCGA) database and the Chinese Glioma Genome Atlas (CGGA) of diffuse glioma patients. Simultaneously, differentially expressed PRGs between TCGA-Glioma tumor samples and the normal brain samples from the Genome Tissue Expression (GTEx) were investigated. Besides, univariate and multivariate Cox regression analysis were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC), Kaplan-Meier curve and principal component analysis (PCA) was undertaken to assess the prognostic capacity of the signature. Gene set enrichment analyses (GSEA) and single sample GSEA (ssGSEA) were used to further understand the molecular mechanisms and the difference of immune microenvironment. External validation of two separate cohorts from the CGGA database was then performed.ResultsCaspase 3 (CASP3) and interleukin-18 (IL18) were identified as potential prognostic biomarkers. A novel prognostic model was constructed to predict diffuse glioma patients' overall survival (OS) time. Patients in high-risk subgroup had shorter survival than those with high-risk with P<0.0001. GSEA and ssGSEA showed the activation of immune-related pathways and the extensive infiltration of immune cells [such as cytotoxic T cells, dendritic cells (DC), natural killer T cell (NKT), induced regulatory T cells (iTreg), naturally occurring regulatory T cells (nTreg)] in high-risk subgroup.ConclusionsA novel two-PRGs prognostic signature based on gene expression was identified, which could predict diffuse glioma patients' OS time. Pyroptosis may be involved in the establishment of immune microenvironment in diffuse glioma.

Project description:As a cold tumor, malignant glioma has strong immunosuppression and immune escape characteristics. The tumor microenvironment (TME) provides the "soil" for the survival of malignant tumors, and cancer-associated fibroblasts (CAFs) are the architects of matrix remodeling in TME. Therefore, CAFs have potent regulatory effects on the recruitment and functional differentiation of immune cells, whereby they synthesize and secrete numerous collagens, cytokines, chemokines, and other soluble factors whose interaction with tumor cells creates an immunosuppressive TME. This consequently facilitates the immune escape of tumor cells. Targeting CAFs would improve the TME and enhance the efficacy of immunotherapy. Thus, regulation of CAFs and CAFs-related genes holds promise as effective immunotherapies for gliomas. Here, by analyzing the Chinese Glioma Genome Atlas and the Cancer Genome Atlas database, the proportion of CAFs in the tumor was revealed to be associated with clinical and immune characteristics of gliomas. Moreover, a risk model based on the expression of CAFs-related six-gene for the assessment of glioma patients was constructed using the least absolute shrinkage and selection operator and the results showed that a high-risk group had a higher expression of the CAFs-related six-genes and lower overall survival rates compared with those in the low-risk group. Additionally, patients in the high-risk group exhibited older age, high tumor grade, isocitrate dehydrogenase wildtype, 1p/19q non-codeletion, O-6-methylguanine-DNA methyltransferase promoter unmethylation and poor prognosis. The high-risk subtype had a high proportion CAFs in the TME of glioma, and a high expression of immune checkpoint genes. Analysis of the Submap algorithm indicated that the high-risk patients could show potent response to anti-PD-1 therapy. The established risk prediction model based on the expression of six CAFs-related genes has application prospects as an independent prognostic indicator and a predictor of the response of patients to immunotherapy.

Dataset Information

Clinical and Biological Significances of a Methyltransferase-Related Signature in Diffuse Glioma.

Publications

Clinical and Biological Significances of a Methyltransferase-Related Signature in Diffuse Glioma.

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