Cuproptosis-related gene-located DNA methylation in lower-grade glioma: Prognosis and tumor microenvironment

Apr 5, 2024Cancer biomarkers : section A of Disease markers

DNA Methylation of Copper-Linked Genes in Lower-Grade Brain Tumors: Links to Patient Outcomes and Tumor Environment

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Abstract

A three CRG-located prognostic signature was validated for lower-grade glioma patients with AUC values of 0.884, 0.888, and 0.859 at 1-year, 3-year, and 5-year intervals in the TCGA dataset.

Cox regression analysis identified the CRG-located DNA-methylation signature as an independent risk factor for lower-grade glioma.
The signature demonstrated associations with immune infiltration levels and immune checkpoints.
Functional enrichment analysis revealed differential involvement in processes like cell differentiation in the hindbrain and glycolysis across risk groups.
Kaplan-Meier survival analysis supported the prognostic value of the DNA-methylation signature in predicting overall survival in lower-grade glioma patients.

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a novel copper-dependent cell death modality, plays a crucial part in the oncogenesis, progression and prognosis of tumors. However, the relationships among located in cuproptosis-related genes (CRGs), overall survival (OS) and the tumor microenvironment remain undefined. In this study, we systematically assessed the prognostic value of CRG-located DNA-methylation for lower-grade glioma (LGG). Clinical and molecular data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We employed Cox hazard regression to examine the associations between CRG-located DNA-methylation and OS, leading to the development of a prognostic signature. Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) analyses were utilized to gauge the accuracy of the signature. Gene Set Enrichment Analysis (GSEA) was applied to uncover potential biological functions of differentially expressed genes between high- and low-risk groups. A three CRG-located DNA-methylation prognostic signature was established based on TCGA database and validated in GEO dataset. The 1-year, 3-year, and 5-year area under the curve (AUC) of ROC curves in the TCGA dataset were 0.884, 0.888, and 0.859 while those in the GEO dataset were 0.943, 0.761 and 0.725, respectively. Cox-regression-analyses revealed the risk signature as an independent risk factor for LGG patients. Immunogenomic profiling suggested that the signature was associated with immune infiltration level and immune checkpoints. Functional enrichment analysis indicated differential enrichment in cell differentiation in the hindbrain, ECM receptor interactions, glycolysis and reactive oxygen species pathway across different groups. We developed and verified a novel CRG-located DNA-methylation signature to predict the prognosis in LGG patients. Our findings emphasize the potential clinical implications of CRG-located DNA-methylation indicating that it may serve as a promising therapeutic target for LGG patients.

Key numbers

0.884

AUC for 1-year OS

Area under the curve for predicting 1-year overall survival in TCGA dataset.

0.888

AUC for 3-year OS

Area under the curve for predicting 3-year overall survival in TCGA dataset.

0.859

AUC for 5-year OS

Area under the curve for predicting 5-year overall survival in TCGA dataset.

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Cuproptosis-related gene-located DNA methylation in lower-grade glioma: Prognosis and tumor microenvironment

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