IFN-α–Stimulated Genes and Epstein-Barr Virus Gene Expression Distinguish WHO Type II and III Nasopharyngeal Carcinomas

Abstract

Nonkeratinizing nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr Virus (EBV) and divided into two subtypes (WHO types II and III) based on histology. We tested whether these subtypes can be distinguished at the molecular genetic level using an algorithm that analyzes sets of related genes (gene set enrichment analysis). We found that a class of IFN-stimulated genes (ISG), frequently associated with the antiviral response, was significantly activated in type III versus type II NPC. Consistent with this, replication of the endogenous EBV was suppressed in type III. A strong association was also seen with a subset of ISGs previously identified in systemic lupus erythematosus, another disease in which 'normal' EBV biology is deregulated, suggesting that this pattern of ISG expression may be linked to the increased EBV activity in both diseases. In contrast, unsupervised hierarchical clustering of the complete expression profiles failed to distinguish the two subsets. These results suggest that type II and III NPC have not originated from obviously distinct epithelial precursors; rather, the histologic differences may be a consequence of a differential antiviral response, involving IFNs, to chronic EBV infection. [Cancer Res 2007;67(2):474-81]

Vesicle‐bound EBV‐BART13‐3p miRNA in circulation distinguishes nasopharyngeal from other head and neck cancer and asymptomatic EBV‐infections

“…We detected low levels of BHRF1-1 miRNA both in tonsil tissues and normal NP brushings, indicative of low level of ongoing viral replication either in plasma cells and/or oropharyngeal epithelial cells lining. This was evident from the NPC brushings, indicative of ongoing viral replication in undifferentiated NPC tumors 45 as we reported previously. 12,45 Thus EBV-BART miRNAs in brushes is a valid option for in situ NPC tumor confirmation after liquid biopsy (cell-free DNA and circulating miRNA) analysis.…”

“…This was evident from the NPC brushings, indicative of ongoing viral replication in undifferentiated NPC tumors 45 as we reported previously. 12,45 Thus EBV-BART miRNAs in brushes is a valid option for in situ NPC tumor confirmation after liquid biopsy (cell-free DNA and circulating miRNA) analysis.…”

BST2 confers cisplatin resistance via NF-κB signaling in nasopharyngeal cancer

“…Consistent with this finding, endogenous EBV replication is suppressed in type III NPC, rendering the virus latent. 39 Thus, we speculate that elevated BST2 expression likely results from latent EBV infection in type III NPC, and that BST2 may have multiple functions in EBV latency, oncogenesis and cisplatin resisitance. However, we did not find differences in BST2 levels between type III and type II NPC, which may be due to the insufficient number of type II samples in this study.…”