IFN-alpha-stimulated genes and Epstein-Barr virus gene expression distinguish WHO type II and III nasopharyngeal carcinomas.
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.
Pegtel
D Michiel
DM
Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA, and Graduate Institute of Microbiology, Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
Subramanian
Aravind
A
Meritt
David
D
Tsai
Ching-Hwa
CH
Sheen
Tzung-Shiahn
TS
Golub
Todd R
TR
Thorley-Lawson
David A
DA
D000465:Algorithms; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics*; D009303:Nasopharyngeal Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D000956:Antigens, Viral; C033305:Epstein-Barr virus early antigen; D016898:Interferon-alpha; D012333:RNA, Messenger