The Epstein-Barr Virus Nuclear Antigen 1 Variant Associated with Nasopharyngeal Carcinoma Defines the Sequence Criteria for Serologic Risk Prediction.

Autor:	Warner BE; Cancer Virology Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.; Cancer Epidemiology and Prevention Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.; Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania., Patel J; Cancer Virology Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.; Department of Biostatistics, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania., Wang R; Cancer Epidemiology and Prevention Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.; Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania., Adams-Haduch J; Cancer Epidemiology and Prevention Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania., Gao YT; Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China., Koh WP; Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore., Wong KW; Department of Pediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Chiang AKS; Department of Pediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Yuan JM; Cancer Epidemiology and Prevention Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.; Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania., Shair KHY; Cancer Virology Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania.; Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Nov 15; Vol. 30 (22), pp. 5207-5217.
DOI:	10.1158/1078-0432.CCR-24-1142
Abstrakt:	Purpose: Antibodies to select Epstein-Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein-Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay. Experimental Design: Mammalian-expressed constructs were developed to represent EBNA1 variants 487V and 487A, which can differ by ≥15 amino acids in the N- and C-termini. Denatured lysates were evaluated by a refined IgA and IgG immunoblot assay in a case-control study using prediagnostic NPC sera from two independent cohorts in Singapore and Shanghai, the People's Republic of China. Results: At 95% sensitivity, 487V yielded a 94.9% specificity compared with 86.1% for 487A. EBNA1 deleted for the conserved glycine-alanine repeats (GAr) reduced false positives by 22.8%. NPC sera reacted more strongly to the C-terminus than healthy controls, but the C-terminal construct (a.a. 390-641) showed lower specificity (84.8%) than the EBNA1 GAr-deleted construct (92.4%) at 95% sensitivity. Conclusions: Although EBNA1 IgA was present in healthy sera, most epitopes localized to the immunodominant GAr. We conclude that a refined EBNA1 antigen deleted for the GAr, but with residues consistently detected in Southeast Asian NPC tumors, is optimized for risk prediction with an extended sojourn time of 7.5 years. Furthermore, distinct EBNA1 serologic profiles enhanced the utility of the EBNA1 IgA assay for risk stratification. This illustrates the importance of serologically relevant EBNA1 sequences for NPC risk prediction and early detection. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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