Glioma is the most common primary brain tumor with poor prognosis and high mortality. The purpose of this study was to use the epigenetic signature to predict prognosis and evaluate the degree of immune infiltration in gliomas. We integrated gene expression profiles and DNA methylation data of lower-grade glioma and glioblastoma to explore epigenetic differences and associated differences in biological function. Cox regression and lasso analysis were used to develop an epigenetic signature based on eight DNA methylation sites to predict prognosis of glioma patients. Kaplan-Meier analysis showed that the overall survival time of high- and low-risk groups was significantly separated, and ROC analysis verified that the model had great predictive ability. In addition, we constructed a nomogram based on age, sex, 1p/19q status, glioma type, and risk score. The epigenetic signature was obviously associated with tumor purity, immune checkpoints, and tumor-immune infiltrating cells (CD8+ T cells, gamma delta T cells, M0 macrophages, M1 macrophages, M2 macrophages, activated NK cells, monocytes, and activated mast cells) and thus, it may find application as a guide for the evaluation of immune infiltration or in treatment decisions in immunotherapy.
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http://dx.doi.org/10.3389/fcell.2021.670854 | DOI Listing |
Background: Despite significant advancements in the development of blood biomarkers for AD, challenges persist due to the complex interplay of genetic and environmental risk factors in AD pathogenesis. Epigenetic processes, including non-coding RNAs and especially microRNAs (miRs), have emerged as important players in the molecular mechanisms underlying neurodegenerative diseases. MiRs have the ability to fine-tune gene expression and proteostasis, and microRNAome profiling in liquid biopsies is gaining increasing interest since changes in miR levels can indicate the presence of multiple pathologies.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, San Diego, San Diego, CA, USA.
Background: Microglia are the major innate immune cells of the brain and play diverse roles in brain development and homeostasis. In the context of Alzheimer's disease, microglia acquire new phenotypes that can exert protective or pathogenic roles. Single cell and single nuclei RNA sequencing experiments have defined molecular signatures of different disease-associated microglia states associated with protective or pathogenic functions, but the mechanisms driving these transitions are not known.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
UK Dementia Research Institute, London, United Kingdom.
Background: Microglia are key players in Alzheimer's disease (AD): Genetic risk for AD is enriched in microglial enhancers, and microglial gene regulatory networks have been shown to be disrupted in AD. Here, we studied polygenic and variant-specific (APOE) risk burden for AD in a xenotransplantation model of AD and human post-mortem brain tissue.
Method: We profiled gene regulation by RNA-seq and ATAC-seq in human iPS-derived microglia, xenotransplanted into the APPNL-G-F mouse model of AD.
Alzheimers Dement
December 2024
Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease that inflicts the elderly worldwide. Recent studies revealed the association of abnormal methylomic alterations in AD. However, a systematic and comprehensive study is needed to investigate the effects of methylomic changes on the molecular networks underpinning AD, in particular, in brain regions most vulnerable to AD neuropathology.
View Article and Find Full Text PDFBackground: Epigenetic mechanisms as a potential underlying pathogenic mechanism of neurodegenerative diseases have been the scope of several studies performed so far. However, there is a gap in analyzing different forms of early-onset dementia to minimize the effect of aging and the use of Lymphoblastoid cell lines (LCLs) as a possible disease model for earlier clinical phases.
Method: We performed a genome-wide DNA methylation analysis in 64 samples (from prefrontal cortex and lymphoblastoid cell lines) from Alzheimer's Disease (AD) and Frontotemporal dementia (FTD) using the Illumina Infinium MethylationEPIC V2.
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