Luo Qingshuang, Long Jingyi, Hu Longtai, Alsaadawe Moyed, Faleti Oluwasijibomi Damola, Lyu Xiaoming
Department of Laboratory Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, China.
The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510630, China.
J Transl Med. 2025 Jun 2;23(1):616. doi: 10.1186/s12967-025-06549-5.
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.
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.
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.
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.
爱泼斯坦-巴尔病毒（EBV）再激活与鼻咽癌（NPC）的不良预后密切相关。然而，NPC进展过程中EBV再激活的分子机制仍不清楚。本研究旨在使用综合多组学方法鉴定参与EBV再激活的关键基因和通路。
建立体外EBV再激活模型以研究与病毒再激活相关的分子变化。进行转录组学（RNA测序）和蛋白质组学（液相色谱-串联质谱）分析以鉴定差异表达基因。进行功能富集、蛋白质-蛋白质相互作用网络分析和生存分析以阐明关键基因的生物学意义。分析NPC患者的RNA测序数据（GSE102349）以评估EBV再激活（BZLF1表达）与临床结局之间的关联。
确定了一个十基因特征（PLAUR、SBSN、LAMC2、CDC42EP1、F3、S100A、CYP24A1、KRT6B、PTGS2和NQO1）与EBV再激活显著相关。这些基因参与上皮-间质转化（EMT）、代谢重编程和缺氧反应。通路分析突出了它们在补体和凝血级联、层粘连蛋白相互作用、角蛋白复合物形成和代谢调节中的作用，所有这些都有助于EMT。此外，对NPC患者数据（GSE102349）的分析揭示了BZLF1表达与不良预后之间的相关性。
本研究通过综合多组学分析鉴定了一种与NPC中EBV再激活相关的新型预后基因特征，这为NPC进展的分子机制提供了见解。这些发现提示了改善NPC的潜在诊断和治疗靶点。
