Epstein-Barr Virus DNA Loads in the Peripheral Blood Cells Predict the Survival of Locoregionally-advanced Nasopharyngeal Carcinoma Patients

Overview

Journal Cancer Biol Med

Specialty Oncology

Date 2021 May 7

PMID 33960178

Citations 6

Authors

Yongqiao He

Dawei Yang

Ting Zhou

Wenqiong Xue

Jiangbo Zhang

Fangfang Li

Fang Wang

Tongmin Wang

Ziyi Wu

Ying Liao

Meiqi Zheng

Changmi Deng

Danhua Li

Yijing Jia

Leilei Yuan

Wenli Zhang

Weihua Jia

Affiliations

Soon will be listed here.

Abstract

Objective: Circulating cell-free Epstein-Barr virus (EBV) DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma (NPC). Despite important insights into the biology of persistence, few studies have addressed the clinical significance of cell-based EBV-DNA loads in peripheral blood cells (PBCs).

Methods: A prospective observational cohort study was conducted involving 1,063 newly diagnosed, locoregionally-advanced NPC patients at Sun Yat-sen University Cancer Center from 2005 to 2007. Cox regression analysis was conducted to identify the association of PBC EBV DNA loads to overall survival (OS) and other prognostic outcomes. Prognostic nomograms were developed based on PBC EBV DNA loads to predict survival outcomes for NPC patients.

Results: After a median follow-up of 108 months, patients with higher PBC EBV-DNA loads had significantly worse OS [hazard ratio (HR) of medium, medium-high, and high low were 1.50, 1.52, and 1.85 respectively; < 0.001]. Similar results were found for progression-free survival and distant metastasis-free survival. The concordance index of the prognostic nomogram for predicting OS in the training set and validation set were 0.70 and 0.66, respectively. Our data showed that the PBC EBV DNA load was an independent and robust survival biomarker, which remained significant even after adjusting for plasma EBV DNA loads in a subset of 205 patients of the cohort (HR: 1.88; = 0.025). Importantly, a combination of PBC EBV DNA load and plasma EBV DNA load improved the predicted OS.

Conclusions: The EBV-DNA load in PBCs may be an independent prognosis marker for NPC patients.

Citing Articles

An overall survival predictive nomogram to identify high-risk patients among locoregionally advanced nasopharyngeal carcinoma: Developed based on the SEER database and validated institutionally.

Lin Y, Chen J, Wang X, Chen S, Yang Y, Hong Y Front Oncol. 2023; 13:1083713.

PMID: 37007141 PMC: 10062447. DOI: 10.3389/fonc.2023.1083713.

Recurrence risk stratification based on Epstein-Barr virus DNA to identify enlarged retropharyngeal lymph nodes of nasopharyngeal carcinoma: A model-histopathologic correlation study.

Mao M, Wang X, Seeruttun S, Chi P, Huang K, Liu W Front Med (Lausanne). 2022; 9:996127.

PMID: 36530897 PMC: 9752871. DOI: 10.3389/fmed.2022.996127.

Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma.

Xu L, Ma Y, Fang C, Peng Z, Gao F, Moll J Front Oncol. 2022; 12:953884.

PMID: 36059644 PMC: 9428750. DOI: 10.3389/fonc.2022.953884.

Epstein-Barr Virus is Associated with Gastric Cancer Precursor: Atrophic Gastritis.

Zhao K, Zhang Y, Xia S, Feng L, Zhou W, Zhang M Int J Med Sci. 2022; 19(5):924-931.

PMID: 35693736 PMC: 9149642. DOI: 10.7150/ijms.71820.

New insights into Epstein‑Barr virus‑associated tumors: Exosomes (Review).

Chen W, Xie Y, Wang T, Wang L Oncol Rep. 2021; 47(1).

PMID: 34779497 PMC: 8600424. DOI: 10.3892/or.2021.8224.

References

Kanakry J, Hegde A, Durand C, Massie A, Greer A, Ambinder R . The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases. Blood. 2016; 127(16):2007-17. PMC: 4841041. DOI: 10.1182/blood-2015-09-672030. View

Babcock G, Decker L, Volk M, Thorley-Lawson D . EBV persistence in memory B cells in vivo. Immunity. 1998; 9(3):395-404. DOI: 10.1016/s1074-7613(00)80622-6. View

Tsao S, Tsang C, Lo K . Epstein-Barr virus infection and nasopharyngeal carcinoma. Philos Trans R Soc Lond B Biol Sci. 2017; 372(1732). PMC: 5597737. DOI: 10.1098/rstb.2016.0270. View

Kanakry J, Ambinder R . The Biology and Clinical Utility of EBV Monitoring in Blood. Curr Top Microbiol Immunol. 2015; 391:475-99. DOI: 10.1007/978-3-319-22834-1_17. View

Tao Q, Chan A . Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments. Expert Rev Mol Med. 2007; 9(12):1-24. DOI: 10.1017/S1462399407000312. View

Kim K, Le Q, Yom S, Ng R, Chan K, Bratman S . Clinical Utility of Epstein-Barr Virus DNA Testing in the Treatment of Nasopharyngeal Carcinoma Patients. Int J Radiat Oncol Biol Phys. 2017; 98(5):996-1001. DOI: 10.1016/j.ijrobp.2017.03.018. View

Gotoh K, Ito Y, Ohta R, Iwata S, Nishiyama Y, Nakamura T . Immunologic and virologic analyses in pediatric liver transplant recipients with chronic high Epstein-Barr virus loads. J Infect Dis. 2010; 202(3):461-9. DOI: 10.1086/653737. View

Wei K, Zheng R, Zhang S, Liang Z, Li Z, Chen W . Nasopharyngeal carcinoma incidence and mortality in China, 2013. Chin J Cancer. 2017; 36(1):90. PMC: 5679327. DOI: 10.1186/s40880-017-0257-9. View

Zhou G, Tang L, Mao Y, Chen L, Li W, Sun Y . Baseline serum lactate dehydrogenase levels for patients treated with intensity-modulated radiotherapy for nasopharyngeal carcinoma: a predictor of poor prognosis and subsequent liver metastasis. Int J Radiat Oncol Biol Phys. 2011; 82(3):e359-65. DOI: 10.1016/j.ijrobp.2011.06.1967. View

10.

Ma B, King A, Lo Y, Yau Y, Zee B, Hui E . Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006; 66(3):714-20. DOI: 10.1016/j.ijrobp.2006.05.064. View

11.

Wang W, Chien Y, Jan J, Lin J . Consistent sequence variation of Epstein-Barr virus nuclear antigen 1 in primary tumor and peripheral blood cells of patients with nasopharyngeal carcinoma. Clin Cancer Res. 2002; 8(8):2586-90. View

12.

Lo Y, Chan A, Chan L, Leung S, Lam C, Huang D . Molecular prognostication of nasopharyngeal carcinoma by quantitative analysis of circulating Epstein-Barr virus DNA. Cancer Res. 2001; 60(24):6878-81. View

13.

Chen H, Ho M, Hu R, Wu J, Chen H, Ni Y . Roles of Epstein-Barr virus viral load monitoring in the prediction of posttransplant lymphoproliferative disorder in pediatric liver transplantation. J Formos Med Assoc. 2019; 118(9):1362-1368. DOI: 10.1016/j.jfma.2018.12.007. View

14.

Klein G . Nasopharyngeal carcinoma (NPC) is an enigmatic tumor. Semin Cancer Biol. 2002; 12(6):415-8. DOI: 10.1016/s1044579x02000834. View

15.

Plummer M, de Martel C, Vignat J, Ferlay J, Bray F, Franceschi S . Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health. 2016; 4(9):e609-16. DOI: 10.1016/S2214-109X(16)30143-7. View

16.

Mao Y, Xie F, Liu L, Sun Y, Li L, Tang L . Re-evaluation of 6th edition of AJCC staging system for nasopharyngeal carcinoma and proposed improvement based on magnetic resonance imaging. Int J Radiat Oncol Biol Phys. 2009; 73(5):1326-34. DOI: 10.1016/j.ijrobp.2008.07.062. View

17.

Thorley-Lawson D, Miyashita E, Khan G . Epstein-Barr virus and the B cell: that's all it takes. Trends Microbiol. 1996; 4(5):204-8. DOI: 10.1016/s0966-842x(96)90020-7. View

18.

Chen Y, Chan A, Le Q, Blanchard P, Sun Y, Ma J . Nasopharyngeal carcinoma. Lancet. 2019; 394(10192):64-80. DOI: 10.1016/S0140-6736(19)30956-0. View

19.

Peng L, Yang Y, Guo R, Mao Y, Xu C, Chen Y . Relationship between pretreatment concentration of plasma Epstein-Barr virus DNA and tumor burden in nasopharyngeal carcinoma: An updated interpretation. Cancer Med. 2018; 7(12):5988-5998. PMC: 6308091. DOI: 10.1002/cam4.1858. View

20.

Gandhi M, Lambley E, Burrows J, Dua U, Elliott S, Shaw P . Plasma Epstein-Barr virus (EBV) DNA is a biomarker for EBV-positive Hodgkin's lymphoma. Clin Cancer Res. 2006; 12(2):460-4. DOI: 10.1158/1078-0432.CCR-05-2008. View