ArticleBrain tumor research and treatment2026
Multi-Layered Dysregulation of NRCAM in Lower-Grade Gliomas: Insights From TCGA Copy Number and Epigenetic Analyses.
Article in Brain tumor research and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Abstract
backgroundNeuronal cell adhesion molecule (NRCAM) has been implicated in glioma biology through splicing alterations reported by prior studies. However, the relative contributions of genomic and epigenetic mechanisms to NRCAM dysregulation in gliomas remain unclear.
methodsWe analyzed data from The Cancer Genome Atlas (TCGA) Lower-Grade Glioma (LGG) cohort using UCSC Xena and cBioPortal. Copy number variation (CNV), DNA methylation (Illumina HumanMethylation450 BeadChip arrays), and mutation profiles were assessed for NRCAM. Kaplan-Meier survival analyses were performed with Xena, stratifying patients by copy number status and methylation state. Correlations between mutation burden and fraction of genome altered (FGA) were evaluated using Spearman and Pearson methods.
resultsSomatic mutations in NRCAM were rare in the TCGA-LGG cohort. In contrast, CNV and methylation changes were frequent and clinically relevant. Copy number gains at the NRCAM locus were associated with significantly shorter overall survival, while higher methylation of NRCAM correlated with improved survival outcomes. NRCAM mutation count did not show a linear correlation with FGA, suggesting these alterations are largely independent of overall genomic instability. The findings highlight copy number imbalance and epigenetic regulation as predominant mechanisms of NRCAM dysregulation.
conclusionNRCAM is recurrently dysregulated in lower-grade gliomas through CNVs and DNA methylation, both of which stratify patient survival. Together with previously reported splicing deregulation, these data suggest that NRCAM functions as a multilayered regulator of glioma progression. NRCAM methylation may represent a potential prognostic biomarker, while therapeutic modulation of NRCAM warrants further investigation.
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