IFN-alpha-stimulated genes and Epstein-Barr virus gene expression distinguish WHO type II and III nasopharyngeal carcinomas.

Cancer Res
Authors
Keywords
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.

Year of Publication
2007
Journal
Cancer Res
Volume
67
Issue
2
Pages
474-81
Date Published
2007 Jan 15
ISSN
0008-5472
URL
DOI
10.1158/0008-5472.CAN-06-1882
PubMed ID
17234754
Links
Grant list
AI 18757 / AI / NIAID NIH HHS / United States
CA 65883 / CA / NCI NIH HHS / United States