EBV Reactivation-associated gene signature predicts poor prognosis in nasopharyngeal carcinoma

Abstract

Background: Epstein-Barr virus (EBV) reactivation is closely associated with poor prognosis in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms underlying EBV reactivation in NPC progression remain unclear. This study aimed to identify key genes and pathways involved in EBV reactivation using an integrated multi-omics approach. Methods: An in vitro EBV reactivation model was established to investigate molecular changes associated with viral reactivation. Transcriptomic (RNA-seq) and proteomic (LC-MS/MS) analyses were performed to identify differentially expressed genes. Functional enrichment, protein-protein interaction network analysis, and survival analysis were conducted to elucidate the biological significance of key genes. RNA-seq data from NPC patients (GSE102349) were analyzed to assess the association between EBV reactivation (BZLF1 expression) and clinical outcomes. Results: A ten-gene signature (PLAUR, SBSN, LAMC2, CDC42EP1, F3, S100A, CYP24A1, KRT6B, PTGS2, and NQO1) was identified as significantly associated with EBV reactivation. These genes are involved in epithelial-mesenchymal transition (EMT), metabolic reprogramming, and hypoxia response. Pathway analysis highlighted their roles in complement and coagulation cascades, laminin interactions, keratin complex formation, and metabolic regulation, all of which contribute to EMT. Additionally, analysis of NPC patient data (GSE102349) revealed a correlation between BZLF1 expression and poor prognosis. Conclusions: This study identifies a novel prognostic gene signature associated with EBV reactivation in NPC through integrated multi-omics analyses, which provided insights into the molecular mechanisms of NPC progression. These findings suggest potential diagnostic and therapeutic targets for improving NPC.