Abstract
<title>Abstract</title> <p> <bold>Background</bold> : Nasopharyngeal carcinoma (NPC) progression is driven by complex transcriptomic and metabolic shifts, including stage-independent downregulation of metabolic clusters and hybrid glycolysis/OXPHOS dynamics (the Warburg effect). However, the upstream epigenetic mechanisms orchestrating these downstream expressions remain poorly understood. <bold>Methods</bold> : Utilizing the NCBI GEO GDS3341 (GSE12452) dataset, we systematically profiled the transcriptomic landscape of 29 core human epigenetic regulators across distinct clinical stages using the R limma framework. <bold>Results</bold> : We identified a highly significant, stage-dependent 6-gene epigenetic signature (DNMT1, EZH2, HDAC2, SMARCA4, BRD4, and H19) dysregulated during regional metastasis. Advanced regional stages (T2N2, T3N2) were characterized by a severe downregulation of the imprinted lncRNA H19 (logFC = -3.16) alongside a robust, concurrent upregulation of chromatin-condensing writers and erasers (EZH2 logFC = 1.52; HDAC2 logFC = 1.05), structural remodeling engines (SMARCA4 logFC = 0.94), and the acetylated histone reader BRD4 (logFC = 0.60). Furthermore, the DNA methylation writer DNMT1 demonstrated early, persistent hyperactivation starting at the T2N1 stage (logFC = 1.52). <bold>Conclusions</bold> : These findings reveal a coordinated, multi-layered epigenetic disruption spanning writers, erasers, readers, and remodelers. We propose that this altered chromatin machinery serves as a higher-level regulatory hub, structurally anchoring the transcriptomic shifts and metabolic reprogramming that drive regional advanced progression in NPC. </p>