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Pathology & Oncology Research

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12.12.2019 | Original Article

Association of Plasma Epstein-Barr Virus LMP1 and EBER1 with Circulating Tumor Cells and the Metastasis of Nasopharyngeal Carcinoma

verfasst von: Le Sun, Yusheng Wang, Jinfeng Shi, Wei Zhu, Xin Wang

Erschienen in: Pathology & Oncology Research | Ausgabe 3/2020

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Abstract

Epstein-Barr virus (EBV) has been widely recognized to contribute to the development of nasopharyngeal carcinoma (NPC). The present study was to explore the association of plasma Epstein-Barr Virus LMP1 and EBER1 with circulating tumor cells (CTCs) and the metastasis of nasopharyngeal carcinoma. In the present study, we quantified the plasma levels of EBV DNA/RNAs, such as LMP1, LMP2, BART and EBER1 with real-time quantitative PCR, and CTCs with a CellSpotter Analyzer in NPC patients, with or without metastasis. Then the correlation of each biomarker with other biomarkers and tumor metastasis was analyzed. Our data indicated that the plasma levels of EBV LMP1, BART, EBER1, along with CTCs were significantly higher in metastatic NPC patients than in non-metastatic patients. Plasma LMP1 DNA and EBER1 discriminate metastatic NPC patients from non-metastatic patients, correlate with tumor stage and node stage for metastatic NPC patients. In summary, there were significantly higher plasma levels of Epstein-Barr Virus DNAs / RNAs in nasopharyngeal carcinoma patients. LMP1 DNA and EBER1 RNA correlated with the metastasis of nasopharyngeal carcinoma.

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108. https://doi.org/10.3322/caac.21262 CrossRefPubMed

Chua M, Wee J, Hui EP, Chan A (2016) Nasopharyngeal carcinoma. Lancet 387:1012–1024. https://doi.org/10.1016/S0140-6736(15)00055-0 CrossRefPubMed

Smatti MK, Al-Sadeq DW, Ali NH, Pintus G, Abou-Saleh H, Nasrallah GK (2018) Epstein-Barr virus epidemiology, serology, and genetic variability of LMP-1 Oncogene among healthy population: an update. Front Oncol 8:211. https://doi.org/10.3389/fonc.2018.00211 CrossRefPubMedPubMedCentral

Pathmanathan R, Prasad U, Sadler R, Flynn K, Raab-Traub N (1995) Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N Engl J Med 333:693–698. https://doi.org/10.1056/NEJM199509143331103 CrossRefPubMed

Liebowitz D (1994) Nasopharyngeal carcinoma: the Epstein-Barr virus association. Semin Oncol 21:376–381PubMed

Tsao SW, Tsang CM, To KF, Lo KW (2015) The role of Epstein-Barr virus in epithelial malignancies. J Pathol 235:323–333. https://doi.org/10.1002/path.4448 CrossRefPubMed

Zou X, You R, Liu H et al (2017) Establishment and validation of M1 stage subdivisions for de novo metastatic nasopharyngeal carcinoma to better predict prognosis and guide treatment. Eur J Cancer 77:117–126. https://doi.org/10.1016/j.ejca.2017.02.029 CrossRefPubMed

Taylor GS, Blackbourn DJ (2011) Infectious agents in human cancers: lessons in immunity and immunomodulation from gammaherpesviruses EBV and KSHV. Cancer Lett 305:263–278. https://doi.org/10.1016/j.canlet.2010.08.019 CrossRefPubMed

Young LS, Arrand JR, Murray PG (2007) EBV gene expression and regulation. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K (eds) Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis, Chapter 27. Cambridge University Press, Cambridge

10.

Lin JC, Wang WY, Chen KY et al (2004) Quantification of plasma Epstein-Barr virus DNA in patients with advanced nasopharyngeal carcinoma. N Engl J Med 350:2461–2470. https://doi.org/10.1056/NEJMoa032260 CrossRefPubMed

11.

Chan AT, Lo YM, Zee B et al (2002) Plasma Epstein-Barr virus DNA and residual disease after radiotherapy for undifferentiated nasopharyngeal carcinoma. J Natl Cancer Inst 94:1614–1619CrossRefPubMed

12.

Chan A, Hui EP, Ngan R et al (2018) Analysis of plasma Epstein-Barr virus DNA in nasopharyngeal Cancer after Chemoradiation to identify high-risk patients for adjuvant chemotherapy: a randomized controlled trial. J Clin Oncol: O2018777847. https://doi.org/10.1200/JCO.2018.77.7847

13.

Lin JC, Wang WY, Liang WM et al (2007) Long-term prognostic effects of plasma epstein-barr virus DNA by minor groove binder-probe real-time quantitative PCR on nasopharyngeal carcinoma patients receiving concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys 68:1342–1348. https://doi.org/10.1016/j.ijrobp.2007.02.012 CrossRefPubMed

14.

Pegtel DM, Middeldorp J, Thorley-Lawson DA (2004) Epstein-Barr virus infection in ex vivo tonsil epithelial cell cultures of asymptomatic carriers. J Virol 78:12613–12624. https://doi.org/10.1128/JVI.78.22.12613-12624.2004 CrossRefPubMedPubMedCentral

15.

Hudnall SD, Ge Y, Wei L, Yang NP, Wang HQ, Chen T (2005) Distribution and phenotype of Epstein-Barr virus-infected cells in human pharyngeal tonsils. Mod Pathol 18:519–527. https://doi.org/10.1038/modpathol.3800369 CrossRefPubMed

16.

Shannon-Lowe C, Adland E, Bell AI, Delecluse HJ, Rickinson AB, Rowe M (2009) Features distinguishing Epstein-Barr virus infections of epithelial cells and B cells: viral genome expression, genome maintenance, and genome amplification. J Virol 83:7749–7760. https://doi.org/10.1128/JVI.00108-09 CrossRefPubMedPubMedCentral

17.

Tao Q, Swinnen LJ, Yang J, Srivastava G, Robertson KD, Ambinder RF (1999) Methylation status of the Epstein-Barr virus major latent promoter C in iatrogenic B cell lymphoproliferative disease. Application of PCR-based analysis. Am J Pathol 155:619–625. https://doi.org/10.1016/S0002-9440(10)65157-7 CrossRefPubMedPubMedCentral

18.

Tong JH, Tsang RK, Lo KW et al (2002) Quantitative Epstein-Barr virus DNA analysis and detection of gene promoter hypermethylation in nasopharyngeal (NP) brushing samples from patients with NP carcinoma. Clin Cancer Res 8:2612–2619PubMed

19.

Cosmopoulos K, Pegtel M, Hawkins J et al (2009) Comprehensive profiling of Epstein-Barr virus microRNAs in nasopharyngeal carcinoma. J Virol 83:2357–2367. https://doi.org/10.1128/JVI.02104-08 CrossRefPubMed

20.

Brooks L, Yao QY, Rickinson AB, Young LS (1992) Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol 66:2689–2697CrossRefPubMedPubMedCentral

21.

Prayongrat A, Chakkabat C, Kannarunimit D, Hansasuta P, Lertbutsayanukul C (2017) Prevalence and significance of plasma Epstein-Barr virus DNA level in nasopharyngeal carcinoma. J Radiat Res 58:509–516. https://doi.org/10.1093/jrr/rrw128 CrossRefPubMedPubMedCentral

22.

Lertbutsayanukul C, Kannarunimit D, Prayongrat A, Chakkabat C, Kitpanit S, Hansasuta P (2018) Prognostic value of plasma EBV DNA for nasopharyngeal Cancer patients during treatment with intensity-modulated radiation therapy and concurrent chemotherapy. Radiol Oncol 52:195–203. https://doi.org/10.2478/raon-2018-0016 CrossRefPubMedPubMedCentral

23.

Kaye KM, Izumi KM, Mosialos G, Kieff E (1995) The Epstein-Barr virus LMP1 cytoplasmic carboxy terminus is essential for B-lymphocyte transformation; fibroblast cocultivation complements a critical function within the terminal 155 residues. J Virol 69:675–683CrossRefPubMedPubMedCentral

24.

Huen DS, Henderson SA, Croom-Carter D, Rowe M (1995) The Epstein-Barr virus latent membrane protein-1 (LMP1) mediates activation of NF-kappa B and cell surface phenotype via two effector regions in its carboxy-terminal cytoplasmic domain. Oncogene 10:549–560PubMed

25.

Turunen A, Rautava J, Grenman R, Syrjanen K, Syrjanen S (2017) Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) associated with poor prognosis of head and neck carcinomas. Oncotarget 8:27328–27338. https://doi.org/10.18632/oncotarget.16033 CrossRefPubMed

26.

Chang Y, Cheng SD, Tsai CH (2002) Chromosomal integration of Epstein-Barr virus genomes in nasopharyngeal carcinoma cells. Head Neck 24:143–150CrossRefPubMed

27.

Kaschka-Dierich C, Adams A, Lindahl T et al (1976) Intracellular forms of Epstein-Barr virus DNA in human tumour cells in vivo. Nature 260:302–306CrossRefPubMed

28.

Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8:329–340. https://doi.org/10.1038/nrc2375 CrossRefPubMed

29.

Lianidou ES, Markou A (2011) Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clin Chem 57:1242–1255. https://doi.org/10.1373/clinchem.2011.165068 CrossRefPubMed

30.

Stevens SJ, Brink AA, Middeldorp JM (2005) Profiling of Epstein-Barr virus latent RNA expression in clinical specimens by gene-specific multiprimed cDNA synthesis and PCR. Methods Mol Biol 292:27–38PubMed

31.

Pavlovitch JH, Didierjean L, Rizk M, Balsan S, Saurat JH (1983) Skin calcium-binding protein: distribution in other tissues. Am J Phys 244:C50–C57. https://doi.org/10.1152/ajpcell.1983.244.1.C50 CrossRef

32.

Ramayanti O, Juwana H, Verkuijlen SA et al (2017) Epstein-Barr virus mRNA profiles and viral DNA methylation status in nasopharyngeal brushings from nasopharyngeal carcinoma patients reflect tumor origin. Int J Cancer 140:149–162. https://doi.org/10.1002/ijc.30418 CrossRefPubMed

33.

Xu YJ, Zhou R, Zong JF et al (2019) Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-kappaB pathway. Cancer Lett 447:33–40. https://doi.org/10.1016/j.canlet.2019.01.022 CrossRefPubMed

34.

Zuo LL, Zhang J, Liu LZ et al (2017) Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma. Oncogenesis 6:402. https://doi.org/10.1038/s41389-017-0005-7 CrossRefPubMedPubMedCentral

35.

Huang D, Song SJ, Wu ZZ et al (2017) Epstein-Barr virus-induced VEGF and GM-CSF drive nasopharyngeal carcinoma metastasis via recruitment and activation of macrophages. Cancer Res 77:3591–3604. https://doi.org/10.1158/0008-5472.CAN-16-2706 CrossRefPubMed

36.

Xie XQ, Luo Y, Ma XL et al (2019) Clinical significance of circulating tumor cells and their expression of cyclooxygenase-2 in patients with nasopharyngeal carcinoma. Eur Rev Med Pharmacol Sci 23:6951–6961. https://doi.org/10.26355/eurrev_201908_18735 CrossRefPubMed

37.

Lee SW, Chen YW, Kuan EC, Lan MY (2019) Dual-function nanostructured platform for isolation of nasopharyngeal carcinoma circulating tumor cells and EBV DNA detection. Biosens Bioelectron 142:111509. https://doi.org/10.1016/j.bios.2019.111509 CrossRefPubMed

38.

You R, Liu YP, Lin M et al (2019) Relationship of circulating tumor cells and Epstein-Barr virus DNA to progression-free survival and overall survival in metastatic nasopharyngeal carcinoma patients. Int J Cancer 145:2873–2883. https://doi.org/10.1002/ijc.32380 CrossRefPubMed

Titel: Association of Plasma Epstein-Barr Virus LMP1 and EBER1 with Circulating Tumor Cells and the Metastasis of Nasopharyngeal Carcinoma
verfasst von: Le Sun
Yusheng Wang
Jinfeng Shi
Wei Zhu
Xin Wang
Publikationsdatum: 12.12.2019
Verlag: Springer Netherlands
Erschienen in: Pathology & Oncology Research / Ausgabe 3/2020
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-019-00777-z

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Springer Medizin

Association of Plasma Epstein-Barr Virus LMP1 and EBER1 with Circulating Tumor Cells and the Metastasis of Nasopharyngeal Carcinoma

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