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The Epstein-Barr virus nuclear antigen 1 variant associated with nasopharyngeal carcinoma defines the sequence criteria for serologic risk prediction.
Warner, Benjamin E; Patel, Japan; Wang, Renwei; Adams-Haduch, Jennifer; Gao, Yu-Tang; Koh, Woon-Puay; Wong, Ka Wo; Chiang, Alan K S; Yuan, Jian-Min; Shair, Kathy H Y.
Afiliación
  • Warner BE; University of Pittsburgh, Pittsburgh, United States.
  • Patel J; University of Pittsburgh, Pittsburgh, PA, United States.
  • Wang R; UPMC Hillman Cancer Center, Pittsburgh, PA, United States.
  • Adams-Haduch J; University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, United States.
  • Gao YT; Shanghai Cancer Institute, Shanghai, China.
  • Koh WP; National University of Singapore, Singapore, Singapore.
  • Wong KW; University of Hong Kong, Hong Kong, Hong Kong, Hong Kong.
  • Chiang AKS; University of Hong Kong, Hong Kong, Hong Kong.
  • Yuan JM; University of Pittsburgh Medical Center, Pittsburgh, PA, United States.
  • Shair KHY; University of Pittsburgh, Pittsburgh, PA, United States.
Clin Cancer Res ; 2024 Sep 12.
Article en En | MEDLINE | ID: mdl-39264275
ABSTRACT

PURPOSE:

Antibodies to select Epstein-Barr virus (EBV) proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against EBV nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years pre-diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay.

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 pre-diagnostic NPC sera from two independent cohorts in Singapore and Shanghai, P.R. China.

RESULTS:

At 95% sensitivity, 487V yielded a 94.9% specificity compared to 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.

CONCLUSION:

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 optimal 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos