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Diagnostic Significance of Combined Detection of Epstein-Barr Virus Antibodies, VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA for Nasopharyngeal Carcinoma

  • Cai, Yong-Lin (Wuzhou Health System Key Laboratory for Nasopharyngeal Carcinoma Etiology and Molecular Mechanism, Wuzhou Red Cross Hospital) ;
  • Li, Jun (Wuzhou Health System Key Laboratory for Nasopharyngeal Carcinoma Etiology and Molecular Mechanism, Wuzhou Red Cross Hospital) ;
  • Lu, Ai-Ying (Wuzhou Health System Key Laboratory for Nasopharyngeal Carcinoma Etiology and Molecular Mechanism, Wuzhou Red Cross Hospital) ;
  • Zheng, Yu-Ming (Wuzhou Health System Key Laboratory for Nasopharyngeal Carcinoma Etiology and Molecular Mechanism, Wuzhou Red Cross Hospital) ;
  • Zhong, Wei-Ming (Department of Oncology, Wuzhou Red Cross Hospital) ;
  • Wang, Wei (Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University) ;
  • Gao, Jian-Quan (Department of Oncology, Wuzhou Red Cross Hospital) ;
  • Zeng, Hong (Wuzhou Health System Key Laboratory for Nasopharyngeal Carcinoma Etiology and Molecular Mechanism, Wuzhou Red Cross Hospital) ;
  • Cheng, Ji-Ru (Wuzhou Health System Key Laboratory for Nasopharyngeal Carcinoma Etiology and Molecular Mechanism, Wuzhou Red Cross Hospital) ;
  • Tang, Min-Zhong (Wuzhou Health System Key Laboratory for Nasopharyngeal Carcinoma Etiology and Molecular Mechanism, Wuzhou Red Cross Hospital)
  • Published : 2014.03.01

Abstract

The objective of this study was to investigate the diagnostic significance of EBV antibody combined detection for nasopharyngeal carcinoma (NPC) in a high incidence region of southern China. Two hundred and eleven untreated NPC patients, 203 non-NPC ENT patients, and 210 healthy controls were recruited for the study. The titers of VCA/IgA and EA/IgA were assessed by immunoenzyme assay, and the levels of Rta/IgG and EBNA1/IgA were determined by enzyme-linked immunosorbent assay. The levels of VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA demonstrated no association with gender or age (p>0.05). The receiver operating characteristic curve and the area under the curve were used to evaluate the diagnostic value. The sensitivity of VCA/IgA (98.1%) and the specificity of EA/IgA (98.5%) were the highest. When a logistic regression model was used to combine the results from multiple antibodies to increase the accuracy, the combination of VCA/IgA+Rta/IgG, whose area under the curve was 0.99, had the highest diagnostic efficiency, and its sensitivity, specificity and Youden index were 94.8%, 98.0% and 0.93 respectively. The data suggest that the combination of VCA/IgA+Rta/IgG may be most suitable for NPC serodiagnosis.

Keywords

References

  1. Bocian J, Januszkiewicz-Lewandowska D (2011). Epstein-Barr virus infection-life cycle, methods of diagnosis, associated diseases. Postepy Hig Med Dosw (Online), 65, 286-98. https://doi.org/10.5604/17322693.943104
  2. Brennan B (2006). Nasopharyngeal carcinoma. Orphanet J Rare Dis, 1, 23. https://doi.org/10.1186/1750-1172-1-23
  3. Burgos JS (2005). Involvement of the Epstein-Barr virus in the nasopharyngeal carcinoma pathogenesis. Med Oncol, 22, 113-21. https://doi.org/10.1385/MO:22:2:113
  4. Cai YL, Zheng YM, Wang W, et al (2010). Combined detection of Epstein-Barr virus antibodies for serodiagnosis of nasopharyngeal carcinoma. Nan Fang Yi Ke Da Xue Xue Bao, 30, 2746-8.
  5. Chen H, Luo YL, Zhang L, et al (2013). EA-D p45-IgG as a potential biomarker for nasopharyngeal carcinoma diagnosis. Asian Pac J Cancer Prev, 14, 7433-8. https://doi.org/10.7314/APJCP.2013.14.12.7433
  6. Cheng WM, Chan KH, Chen HL, et al (2002). Assessing the risk of nasopharyngeal carcinoma on the basis of EBV antibody spectrum. Int J Cancer Suppl, 97, 489-92. https://doi.org/10.1002/ijc.1641
  7. Chien YC, Chen JY, Liu MY, et al (2001). Serologic markers of Epstein-Barr virus infection and nasopharyngeal carcinoma in Taiwanese men. N Engl J Med, 345, 1877-82. https://doi.org/10.1056/NEJMoa011610
  8. Deng H, Zeng Y, Lei Y, et al (1995). Serological survey of nasopharyngeal carcinoma in 21 cities of south China. Chin Med J, 108, 300-3.
  9. Fachiroh J, Paramita DK, Hariwiyanto B, et al (2006). Singleassay combination of Epstein-Barr Virus (EBV) EBNA1-and viral capsid antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G (IgG) and IgA antibody levels in sera from nasopharyngeal carcinoma patients: options for field screening. J Clin Microbiol, 44, 1459-67. https://doi.org/10.1128/JCM.44.4.1459-1467.2006
  10. Feng P, Ren EC, Liu D, Chan SH, Hu H (2000). Expression of Epstein-Barr virus lytic gene BRLF1 in nasopharyngeal carcinoma: potential use in diagnosis. J Gen Virol, 81, 2417-23.
  11. Feng P, Chan SH, Soo MY, et al (2001). Antibody response to Epstein-Barr virus Rta protein in patients with nasopharyngeal carcinoma: a new serologic parameter for diagnosis. Cancer, 92, 1872-80. https://doi.org/10.1002/1097-0142(20011001)92:7<1872::AID-CNCR1704>3.0.CO;2-N
  12. Han BL, Xu XY, Zhang CZ, et al (2012). Systematic review on Epstein-Barr virus (EBV) DNA in diagnosis of nasopharyngeal carcinoma in Asian populations. Asian Pac J Cancer Prev, 13, 2577-81. https://doi.org/10.7314/APJCP.2012.13.6.2577
  13. Hariwiyanto B, Sastrowiyoto S, Mubarika S, Salugu M (2010). LMP1 and LMP2 may be prognostic factors for outcome of therapy in nasopharyngeal cancers in Indonesia. Asian Pac J Cancer Prev, 11, 763-6.
  14. Hu B, Hong G, Li Z, et al (2007). Expression of VCA (viral capsid antigen) and EBNA1 (Epstein-Barr-virus-encoded nuclear antigen 1) genes of Epstein-Barr virus in Pichia pastoris and application of the products in a screening test for patients with nasopharyngeal carcinoma. Appl Biochem Biotechnol, 47, 59-69. https://doi.org/10.1042/BA20060153
  15. Huang TR, Zhang SW, Chen WQ, et al (2012). Trends in nasopharyngeal carcinoma mortality in China, 1973-2005. Asian Pac J Cancer Prev, 13, 2495-502. https://doi.org/10.7314/APJCP.2012.13.6.2495
  16. Jia WH, Huang QH, Liao J, et al (2006). Trends in incidence and mortality of nasopharyngeal carcinoma over a 20-25 year period (1978/1983-2002) in Sihui and Cangwu counties in southern China. BMC Cancer, 6, 178. https://doi.org/10.1186/1471-2407-6-178
  17. Leung SF, Tam JS, Chan AT, et al (2004). Improved accuracy of detection of nasopharyngeal carcinoma by combined application of circulating Epstein-Barr virus DNA and anti-Epstein-Barr viral capsid antigen IgA antibody. Clin Chem, 50, 339-45. https://doi.org/10.1373/clinchem.2003.022426
  18. Li HF, Zhong JM, Liao J (2007). Detection of EB virus IgA/VCA, IgA/EA and IgG/EA antibodies in nasopharyngeal carcinoma diagnosis. Guangxi Med J, 29, 500-1.
  19. Liu P, Speck SH (2003). Synergistic autoactivation of the Epstein-Barr virus immediate-early BRLF1 promoter by Rta and Zta. Virology, 310, 199-206. https://doi.org/10.1016/S0042-6822(03)00145-4
  20. Liu Y, Huang Q, Liu W, et al (2012). Establishment of VCA and EBNA1 IgA-based combination by enzyme-linked immunosorbent assay as preferred screening method for nasopharyngeal carcinoma: a two-stage design with a preliminary performance study and a mass screening in southern China. Int J Cancer Suppl, 131, 406-16. https://doi.org/10.1002/ijc.26380
  21. Niedobitek G (2000). Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Mol Pathol, 53, 248-54. https://doi.org/10.1136/mp.53.5.248
  22. Raab-Traub N (2002). Epstein-Barr virus in the pathogenesis of NPC. Semin Cancer Biol, 12, 431-41. https://doi.org/10.1016/S1044579X0200086X
  23. Ragoczy T, Heston L, Miller G (1998). The Epstein-Barr virus Rta protein activates lytic cycle genes and can disrupt latency in B lymphocytes. J Virol, 72, 7978-84.
  24. Ren J, Zhang MX, Zhang GX, et al (2006). Studies on antibody response to recombinant Rta protein in patient with nasopharyngeal carcinoma. Chin J Microbiol Immunol, 26, 1057-9.
  25. Tang M, Zeng Y, Poisson A, et al (2010). Haplotype-dependent HLA susceptibility to nasopharyngeal carcinoma in a Southern Chinese population. Genes Immun, 11, 334-42. https://doi.org/10.1038/gene.2009.109
  26. Tang M, Lautenberger JA, Gao X, et al (2012). The principal genetic determinants for nasopharyngeal carcinoma in china involve the hla class i antigen recognition groove. PLoS Genet, 8, 1003103. https://doi.org/10.1371/journal.pgen.1003103
  27. Tao Q, Srivastava G, Chan AC, et al (1995). Evidence for lytic infection by Epstein-Barr virus in mucosal lymphocytes instead of nasopharyngeal epithelial cells in normal individuals. J Med Virol, 45, 71-7. https://doi.org/10.1002/jmv.1890450114
  28. Walling DM, Flaitz CM, Nichols CM, Hudnall SD, Adler-Storthz K (2001). Persistent productive Epstein-Barr virus replication in normal epithelial cells in vivo. J Infect Dis, 184, 1499-507. https://doi.org/10.1086/323992
  29. Wen S, Mizugaki Y, Shinozaki F, Takada K (1997). Epstein-Barr virus (EBV) infection in salivary gland tumors: lytic EBV infection in nonmalignant epithelial cells surrounded by EBV-positive T-lymphoma cells. Virology, 227, 484-7. https://doi.org/10.1006/viro.1996.8352
  30. Xue SA, Lu QL, Poulsom R, et al (2000). Expression of two related viral early genes in Epstein-Barr virus-associated tumors. J Virol, 74, 2793-803. https://doi.org/10.1128/JVI.74.6.2793-2803.2000
  31. Yu KJ, Hsu WL, Pfeiffer RM, et al (2011). Prognostic utility of anti-EBV antibody testing for defining NPC risk among individuals from high-risk NPC families. Clin Cancer Res, 17, 1906-14. https://doi.org/10.1158/1078-0432.CCR-10-1681
  32. Zhan SB, Zhong JM, Mai ZP, et al (2009). Improve on serological diagnosis method of nasopharyngeal carcinoma. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 23, 65-7.
  33. Zhang JX, Chen HL, Zong YS, et al (1998). Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma. J Med Virol, 55, 227-33. https://doi.org/10.1002/(SICI)1096-9071(199807)55:3<227::AID-JMV8>3.0.CO;2-3

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